Proteopedia - User contributions [en]

Poly(A) Polymerase

2016-04-03T03:17:37Z

Eran Hodis:

[[Image:2q66.png|left|170px]]
==Function==

[[Poly(A) Polymerase]] (polynucleotide adenylytransferase, [[EC Number|EC]] 2.7.7.19) is the enzyme responsible for adding a polyadenine tail to the 3' end of a nascent pre-mRNA transcript. Its substrates are ATP and RNA. The poly(A) tail that poly-A polymerase adds to the 3' end of the pre-mRNA transcript is important for nuclear export, translation and stability of the mRNA.

==Determinants of ATP Recognition==
<StructureSection load='2q66' scene='Proteopedia:Main_page_develop/2q66_initial/3' size='350' side='right' caption='Structure of Yeast Poly(A) Polymerase with ATP, Mg+2 ion (green) and oligo(A) (PDB entry [[2q66]])'>
Poly(A) Polymerase binds specifically to ATP and adds it at the end of a messenger RNA chain. This structure contains an oligo(A) polynucleotide with five nucleotides, an ATP molecule, and a magnesium ion. The enzyme is an inactive mutant with the catalytic aspartate 154 changed to alanine. Poly(A) polymerase normally has a second magnesium ion, but that second magnesium ion is absent from this structure due to the inactivating mutation D154A. In the <scene name='2q66/2q66_summary/1'>summary picture</scene>, the enzyme is in blue backbone representation, the RNA chain is in yellow, the ATP is in red, the magnesium is in green, and ALA154 is in magenta. Several mechanisms are used to achieve the specificity for ATP. The magnesium is coordinated by <scene name='2q66/2q66_asp/2'>ASP100 and ASP102</scene>, and the magnesium coordinates with the phosphates of ATP, positioning the nucleotide in the active site. The adenine base is sandwiched between the <scene name='2q66/2q66_stacking/2'>terminal base of the RNA (in yellow) and VAL234 (in cyan)</scene>. Surprisingly, there are very few contacts with the hydrogen-bonding groups in the adenine base. <scene name='2q66/2q66_asn/1'>ASN 226</scene> may form a [[hydrogen bond]] to adenine in the active enzyme, but the distance is a bit too long in this mutant structure. Instead of forming specific hydrogen bonds with the enzyme, most of the hydrogen-bonding groups in the base, sugar and phosphate interact with a shell of <scene name='Goodsell_Sandbox/2q66_water/2'>buried water molecules</scene>. Discrimination between ATP and GTP is achieved through a close steric contact between the <scene name='2q66/2q66_c2/2'>adenine C2 (in white) and the sidechains of THR 304 and MET310 (shown in cyan)</scene>. Guanine bases have an extra amino group at this position that would be too bulky to fit against these amino acids.
</StructureSection>

<blockquote>
This section complements the article on [http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb106_1.html Poly(A) Polymerase] in the
[http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] Series. See also [[Teaching Scenes, Tutorials, and Educators' Pages]].
</blockquote>

==3D structures of poly(A) polymerase==

Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|

*Poly(A) polymerase

**[[3aqk]], [[3aql]], [[3aqm]], [[3aqn]] – PAP residues 18-431 – ''Escherichia coli'' 
**[[2hhp]], [[2o1p]] – yPAP - yeast 
**[[1q79]], [[1f5a]] - bPAP-α - bovine 
**[[4lt6]] – hPAP-Υ – human 
**[[3pq1]] – hPAP 
**[[3owg]] – VvPAP catalytic subunit – Vaccinia virus 
**[[3wfo]], [[3wfp]], [[4wby]], [[4wbz]] – AaPAP – ''Aquifex aeolicus'' 

*Poly(A) polymerase complex with RNA

**[[3er8]], [[3er9]], [[3erc]] – VvPAP VP55 + RNA 
**[[1av6]] - VvPAP VP39 + SAH + RNA 
**[[3wfq]], [[3wfr]], [[3wfs]], [[4wc3]], [[4wc4]] [[4wc5]], [[4wc6]], [[4wc7]], [[4x0a]]. [[4x0b]] - AaPAP + RNA 
**[[4wc2]] - AaPAP + RNA + ATP analog 

*Poly(A) polymerase other complexes

**[[2ga9]] - VvPAP VP55 + VP39 + ATP 
**[[2gaf]] - VvPAP VP55 (mutant) + VP39 
**[[1jtf]], [[2vp3]] - VvPAP VP39 residues 1-307 (mutant) + M7GPPPG + SAH 
**[[1b42]], [[1bky]], [[1eqa]], [[3mag]], [[3mct]], [[4dcg]], [[1av6]], [[1p39]], [[1v39]]. [[1jsz]] - VvPAP VP39 residues 1-297 (mutant) + purine derivative + SAH 
**[[1vp3]] - VvPAP VP39 + SAH 
**[[1vp9]], [[1eam]], [[1jte]] - VvPAP VP39 (mutant) + SAH 
**[[1vpt]] - VvPAP VP39 (mutant) + SAM 
**[[3c66]] - yPAP residues 1-526 + Fip1 peptide 
**[[2q66]] – yPAP + polyA + ATP 
**[[1fa0]] - yPAP + Mn + ATP 
**[[1q78]] – bPAP-α + Mg + ATP 
**[[4wc0]], [[4wc1]] - AaPAP + nucleotide 
}}

Note: the regulatory subunit of Vaccinia virus Poly(A) polymerase is called '''VP39''' and the catalytic subunit name is '''VP55'''

==Additional Resources==
For additional information, see: [[Translation]] 
For additional examples of transferases, see: [[Transferase]]

*PDB entry [[2q66]]

==Reference==
Mechanism of poly(A) polymerase: structure of the enzyme-MgATP-RNA ternary complex and kinetic analysis., Balbo PB, Bohm A, Structure. 2007 Sep;15(9):1117-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17850751 17850751]
[[Category:Topic Page]]
[[Category: Polynucleotide adenylyltransferase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Balbo, P.]]
[[Category: Bohm, A.]]
[[Category: Protein rna complex atp polymerase complex]]
[[Category: Transferase/rna complex]]
[[Category: RCSB PDB Molecule of the Month]]

Poly(A) Polymerase

2016-04-02T02:30:41Z

Eran Hodis:

User:Eran Hodis

2014-12-25T23:16:47Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab] and [https://www.broadinstitute.org/scientific-community/science/core-faculty-labs/regev-lab/regev-lab-home Aviv Regev's lab]. I research and study the somatic genetics of cancer, particularly melanoma. Previously, I studied computational biology as a graduate student at the Weizmann Institute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab] focusing on transcriptional regulation in yeast. I'm one of the co-creators of Proteopedia -- this website, a 3D encyclopedia of protein structures -- together with [[User:Joel L. Sussman|Joel L. Sussman]] and [[User:Jaime Prilusky|Jaime Prilusky]] at the Weizmann Institute of Science.

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID: 25344691</ref><ref group='xtra'>PMID: 25294245</ref><ref group='xtra'>PMID: 25079552</ref><ref group='xtra'>PMID:24625776</ref><ref group='xtra'>PMID:24265154</ref><ref group='xtra'>PMID:24265153</ref><ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2014-11-08T18:52:51Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab] and [https://www.broadinstitute.org/scientific-community/science/core-faculty-labs/regev-lab/regev-lab-home Aviv Regev's lab]. I research and study the somatic genetics of cancer, particularly melanoma. Previously, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab] focusing on transcriptional regulation in yeast. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID: 25344691</ref><ref group='xtra'>PMID: 25294245</ref><ref group='xtra'>PMID: 25079552</ref><ref group='xtra'>PMID:24625776</ref><ref group='xtra'>PMID:24265154</ref><ref group='xtra'>PMID:24265153</ref><ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2014-08-11T05:34:07Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab] and [https://www.broadinstitute.org/scientific-community/science/core-faculty-labs/regev-lab/regev-lab-home Aviv Regev's lab]. I research and study the somatic genetics of cancer, particularly melanoma. Previously, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab] focusing on transcriptional regulation in yeast. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID: 25079552</ref><ref group='xtra'>PMID:24625776</ref><ref group='xtra'>PMID:24265154</ref><ref group='xtra'>PMID:24265153</ref><ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2014-08-11T05:31:23Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab] and [https://www.broadinstitute.org/scientific-community/science/core-faculty-labs/regev-lab/regev-lab-home Aviv Regev's lab]. I research and study the somatic genetics of cancer, particularly melanoma. Previously, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab] focusing on transcriptional regulation in yeast. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2013-10-28T04:35:58Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I have carried out research on the somatic genetics of melanoma at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab] focusing on transcriptional regulation in yeast. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2013-09-24T18:24:51Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma from a somatic genomic perspective at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID:23770567</ref><ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2013-09-02T17:15:29Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma from a somatic genomic perspective at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname_lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2013-04-01T02:33:33Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma from a somatic genomic perspective at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at firstname.lastname@hms.harvard.edu

==Publications==
<ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2013-01-27T07:04:08Z

Eran Hodis: /* Publications */

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma from a somatic genomic perspective at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:23348506</ref><ref group='xtra'>PMID:23166030</ref><ref group='xtra'>PMID:22987558</ref><ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2012-11-06T05:10:31Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma from a somatic genomic perspective at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2012-11-06T05:09:14Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me -- I research melanoma somatic genomics at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2012-11-06T05:02:47Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. The somatic genetics of cancer fascinates me. I research melanoma somatic genomics at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Before that, I studied computational biology as a graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia (this site, a 3D encyclopedia of protein structures).

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

User:Eran Hodis

2012-09-30T17:28:38Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. Previously I researched melanoma genomics as an associate computational biologist at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. And, before that, I was a computational biology graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia.

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22980975</ref><ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

==My Working Area==
* [[User:Eran_Hodis/Workbench]]
* [[User:Eran_Hodis/Sandbox]]
* [[User:Eran_Hodis/Sandbox1]]
* [[User:Eran_Hodis/Sandbox2]]
* [[User:Eran_Hodis/Sandbox3]]
* [[User:Eran_Hodis/Sandbox4]]
* [[User:Eran_Hodis/Sandbox5]]
* [[User:Eran_Hodis/Sandbox6]]
* [[User:Eran_Hodis/Sandbox7]]
* [[User:Eran_Hodis/Sandbox8]]
* [[User:Eran_Hodis/Sandbox PPT]]
* [[User:Eran_Hodis/Sandbox Main Page]]
* [[User:Eran_Hodis/P2J]]
* [[User:Eran_Hodis/1ea5_test]]

User:Eran Hodis

2012-08-05T20:17:36Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an MD-PhD student at Harvard Medical School and MIT. Previously I researched melanoma genomics as an associate computational biologist at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. And, before that, I was a computational biology graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia.

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22817889</ref><ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

==My Working Area==
* [[User:Eran_Hodis/Workbench]]
* [[User:Eran_Hodis/Sandbox]]
* [[User:Eran_Hodis/Sandbox1]]
* [[User:Eran_Hodis/Sandbox2]]
* [[User:Eran_Hodis/Sandbox3]]
* [[User:Eran_Hodis/Sandbox4]]
* [[User:Eran_Hodis/Sandbox5]]
* [[User:Eran_Hodis/Sandbox6]]
* [[User:Eran_Hodis/Sandbox7]]
* [[User:Eran_Hodis/Sandbox8]]
* [[User:Eran_Hodis/Sandbox PPT]]
* [[User:Eran_Hodis/Sandbox Main Page]]
* [[User:Eran_Hodis/P2J]]
* [[User:Eran_Hodis/1ea5_test]]

P53-DNA Recognition

2012-07-07T13:25:17Z

Eran Hodis:

''This is a joint project of La Canada High School and University of Southern California students, mentored by Professor Remo Rohs.''

=A Base Pairing Variant Enhances p53 Binding to a Consensus Sites=

==Introduction and Biological Role of the Tumor Suppressor p53==

[[Image:p53-intro.jpg|thumb|left|300px|Figure 1: Crystal structure of a p53 DBD tetramer-DNA complex; [http://www.rcsb.org/pdb/explore/explore.do?structureId=3kz8 PDB ID# 3KZ8]<ref name='kitayner'>Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol. 2010;17(4):423-9.</ref>.]]

[[Image:consensus.jpg|thumb|right|250px|Figure 2: p53 consensus site; R= A or G, Y= C or T, and W=A or T.]]

[[Image:p53-domains.jpg|thumb|right|400px|Figure 3: Frequency of p53 mutants associated with cancer derived from [http://www-p53.iarc.fr/ IARC TP53 database]. Domain architecture; N-ter=N-terminal, DBD=DNA binding domain<ref name='kitayner'/>, Tet=Tetramerization<ref name='tetra'>Jeffrey PD, Gorina S, Pavletich NP. Crystal structure of the p53 tetramerization domain. Science 1995;267:1498-502.</ref>, and C-ter=C-terminal domain. Intermediate regions are fairly disordered.]]

Also known as the '''Guardian of the Genome''', the tumor suppressor p53 is central in the natural defense against human cancer. The protein is activated by stress factors that can compromise the genomic integrity of the cell, and this activation unleashes the function of p53 as transcription factor. It binds as a tetramer (Figure 1) to a large range of DNA response elements. The p53 consensus site (Figure 2) is formed by two decameric half-sites, each containing a core element (red), that are separated by a variable number of base pairs (blue).

Binding of p53 to different response elements leads to distinct biological responses, such as cell-cycle arrest, senescence, or apoptosis. These different pathways correspond, at least in part, to differences in p53-DNA binding affinity and stability, which are determined by specific protein-DNA interactions.

Mutations of p53 residues are associated with 50% of human cancers. Such mutations are predominantly located in the p53-DNA binding domain (DBD) based on an analysis of human tumors (Figure 3). Particularly, arginine residues in the p53-DNA interface were found in tumors with high frequencies.

==Structural Description of p53-DNA Complex==

===Domain Architecture and Tetramerization===

<Structure load='P53tetra.pdb.zip' size='250' frame='true' align='left' caption='Figure 4: Crystal structure of p53 tetramerization domain, [http://www.rcsb.org/pdb/explore.do?structureId=1c26 PDB ID 1C26].' scene='Sandbox_Reserved_170/Tetra/2' />

<Structure load='3kz8bio-4mon.pdb.zip' size='500' frame='true' align='right' caption='Figure 5: Crystal structure of p53 DBD tetramer-DNA complex, PDB ID 3KZ8.' scene='Sandbox_Reserved_170/Complex/6' />

The p53 protein consists of the N-terminal transactivation, the DNA binding or core, the tetramerization, and the C-terminal regulatory domain (Figure 3). This Proteopedia page discusses protein-DNA recognition by p53, thus focuses on the DBD of p53. The only other domain for which structural information is available is the <scene name='Sandbox_Reserved_170/Tetra/1'>tetramerization domain</scene>, which forms as a dimer of dimers with one alpha helix and one beta strand contributed by each p53 monomer.

The <scene name='Sandbox_Reserved_170/Complex/6'>DBD in tetrameric form binds to a response element</scene>, which consists of two half sites. These decameric half sites can be separated by a spacer of flexible length but in this case the spacer is of length zero base pairs. The <scene name='Sandbox_Reserved_170/Complex/7'>p53 tetramer binds DNA as a dimer of dimers</scene> with each dimer binding to one half site of the response element.

The p53 DBD assumes the conformation of an <scene name='Sandbox_Reserved_170/Beta/1'>immunoglobulin-like fold consisting of a beta sandwich</scene>, which binds the response element in the major groove. A functionally important <scene name='Sandbox_Reserved_170/Zn/1'>Zn2+ ion coordinates the Cys176, His179, Cys238, Cys242 residues</scene> and, thus, stabilizes the fold of the DBD.

===Protein-Protein Interactions===

The p53 tetramer forms a relatively small <scene name='Sandbox_Reserved_170/Intra-dimer/4'>intra-dimer interface with two salt bridges between Glu180 and Arg181 residues</scene> and, in comparison, a large <scene name='Sandbox_Reserved_170/Inter-dimer/4'>inter-dimer interface with an extensive network of interactions</scene>. The actual molecular interactions and strength in binding can vary as a function of the sequence and spacer length of the response element.

===Major Groove Base Readout===

[[Image:p53-motif.jpg|thumb|right|300px|Figure 6: p53 binding site motif with G/C base pairs most conserved. PLoS has provided permission for usage of this figure.]]

Protein side chains and base pairs form direct contacts in the major groove among which the <scene name='Sandbox_Reserved_170/Arg280_contact/5'>contact between Arg280 and the guanine of the core element</scene> contributes most to binding specificity. This highly specific readout is due to the <scene name='Sandbox_Reserved_170/Arg280_contact/4'>bidentate hydrogen bond formed between Arg280 and guanine</scene>. As a result of this '''base readout''' the G/C base pairs in the CWWG core elements are the most conserved positions in p53 response elements (Figure 6).

Another important contact is formed with the <scene name='Sandbox_Reserved_170/Lys_120/3'>Lys120 residue from the L1 loop of the protein</scene>. Lys120 is biologically very important because acetylation of this residue is known to trigger the apoptotic response of p53.

===DNA Backbone Contact===

Another arginine residue, <scene name='Sandbox_Reserved_170/Arg273/2'>Arg273, contacts the phosphodiester backbone</scene> and seems to be important for p53-DNA binding. Moreover, Arg273 is the second most common missense mutation in human cancer (Figure 2).

[[Image:Kitayner-etal-Figure7.jpg|thumb|right|400px|Figure 7: DNA shape readout of narrow minor groove regions with enhanced electrostatic potential by Arg248<ref name='kitayner'/>. Nature Publishing Group has provided permission for usage of this figure.]]

===Minor Groove Shape Readout===

Most commonly, however, the residue Arg248 is found mutated in human tumors. <scene name='Sandbox_Reserved_170/Arg248/2'>Arg248 contacts the minor groove</scene> although it does not usually form hydrogen bonds with the bases. Arg248 was shown to recognize regions of narrow minor groove associated with enhanced negative electrostatic potential (Figure 7)<ref name='kitayner'/>. This observation provides a novel molecular explanation of the importance of Arg248 for p53-DNA binding and its role in cancer. The described mechanism known as '''shape readout''' was found to be broadly employed by arginine residues<ref name="nature">Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. The role of DNA shape in protein-DNA recognition. Nature. 2009;461(7268):1248-53.</ref>.

==Hoogsteen vs. Watson-Crick Base Pair in p53 Binding Sites==

The distinct <scene name='Sandbox_Reserved_170/Arg248/2'>shape of the minor groove recognized by Arg248</scene> is due to a transition of the four A/T base pairs of the CATG core elements to a Hoogsteen base pairing geometry. Regions with Hoogsteen base pairs (green) <scene name='Sandbox_Reserved_170/Hg_helix/2'>decrease the diameter of the double helix</scene> compared to regions with Watson-Crick base pairs (blue).

The reason for this deformation of the double helix is the <scene name='Group:USC-LCHS/3kz8_ba_hoogsteencloseup/2'>base pairing geometry in Hoogsteen base pairs</scene> with the approximately 180 degree rotation of adenine around the glycosidic bond and formation of hydrogen bonds with thymine at a different edge of the adenine base compared to <scene name='Group:USC-LCHS/3kmd_wcbp_closeup/1'>standard Watson-Crick base pairing</scene>, depicted here for the identical base pair in a p53 response element with different sequence from [[3kmd|PDB ID# 3KMD]].

=Further Reading=

Hoogsteen base pairs have previously been found in protein-DNA complexes but usually associated with drastic deformations of the DNA. Only in one case of a homeodomain protein, a Hoogsteen base pair was identified in undistorted B-DNA<ref name="wolberger">Aishima J, Gitti RK, Noah JE, Gan HH, Schlick T, Wolberger C. A Hoogsteen base pair embedded in undistorted B-DNA. Nucleic Acids Res. 2002;30(23):5244-52.</ref>.

As for p53-DNA recognition, Hoogsteen base pairs are not present in the complex with a different DNA sequence <ref name="chen">Chen Y, Dey R, Chen L. Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer. Structure. 2010;18(2):246-56.</ref> but the DNA undergoes a different deformation not observed in the complex with Hoogsteen base pairing. Since transient Hoogsteen base pairs have been detected in naked DNA with preferences for CA and TA dincucleotides<ref name="hashimi">Nikolova EN, Kim E, Wise AA, O'Brien PJ, Andricioaei I, Al-Hashimi HM. Transient Hoogsteen base pairs in canonical duplex DNA. Nature. 2011;470(7335):498-502.</ref>, the observation of the base pairing variant in p53-DNA complexes indicates a sequence-speific feature of the response element either recognized or stabilized by p53.

A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69.</ref>. 

=Acknowledgements=
This Proteopedia page originates from the partnership of the Rohs Laboratory at the University of Southern California with La Canada High School. This partnership was initiated by Remo Rohs and Patty Compeau in September 2011 as '''Bioinformatics Institute''', which is part of the Institutes of the 21st Century. Contributors to this page are USC graduate students Ana Carolina Dantas Machado, Proteopedia editor Eran Hodis, and La Canada High School students (xxx).

Research presented on this page has been conducted in the Shakked Lab at the Weizmann Institute of Science, and the Honig Lab at Columbia University. and the Rohs and L. Chen Labs at USC. Furthermore, technical help by Proteopedia editors Eran Hodis, Eric Martz, Jaime Prilusky, and Joel Sussman is acknowledged. 

=References=
<references/>

User:Eran Hodis

2012-05-27T18:30:54Z

Eran Hodis:

__NOTOC__

[[Image:Eran_Hodis.jpg|thumb|right|400px|Eran Hodis on the campus of the Weizmann Institute of Science in April of 2008]]

I am an associate computational biologist at the Broad Institute and the Dana-Farber Cancer Institute in [http://garrawaylab.dfci.harvard.edu/ Levi Garraway's lab]. Previously I was a computational biology graduate student at the Weizmann Insitute of Science in [http://genie.weizmann.ac.il/ Eran Segal's lab]. I'm one of the co-creators of Proteopedia and the developer of the [http://www.weizmann.ac.il/ISPC/eMovie.html eMovie] PyMOL plug-in for macromolecular movie-making.

Contact me at <email>eran.hodis@weizmann.ac.il</email>

==Publications==
<ref group='xtra'>PMID:22622578</ref><ref group='xtra'>PMID: 21567857 </ref><ref group='xtra'>PMID:21536137</ref><ref group='xtra'>PMID:20841429</ref><ref group='xtra'>PMID:19230677</ref><ref group='xtra'>PMID:18854127</ref><ref group='xtra'>PMID:18673581</ref><ref group='xtra'>PMID:17448663</ref>
<references group='xtra'/>

{{Clear}}

==My Working Area==
* [[User:Eran_Hodis/Workbench]]
* [[User:Eran_Hodis/Sandbox]]
* [[User:Eran_Hodis/Sandbox1]]
* [[User:Eran_Hodis/Sandbox2]]
* [[User:Eran_Hodis/Sandbox3]]
* [[User:Eran_Hodis/Sandbox4]]
* [[User:Eran_Hodis/Sandbox5]]
* [[User:Eran_Hodis/Sandbox6]]
* [[User:Eran_Hodis/Sandbox7]]
* [[User:Eran_Hodis/Sandbox8]]
* [[User:Eran_Hodis/Sandbox PPT]]
* [[User:Eran_Hodis/Sandbox Main Page]]
* [[User:Eran_Hodis/P2J]]
* [[User:Eran_Hodis/1ea5_test]]

MEK1

2011-12-31T21:36:36Z

Eran Hodis: Redirecting to Mitogen-activated protein kinase kinase

#REDIRECT [[Mitogen-activated protein kinase kinase]]

MAP2K1

2011-12-31T21:36:17Z

Eran Hodis: Redirecting to Mitogen-activated protein kinase kinase

#REDIRECT [[Mitogen-activated protein kinase kinase]]

Template:MainPageProteopediaReferences

2011-12-12T16:01:58Z

Eran Hodis:

[[Image:Genome Biology.png|right|150px]]
[http://genomebiology.com/2008/9/8/R121 ''Genome Biology'' '''2008'''], and in '''2011''': ''Proteopedia: A status report on the collaborative, 3D web-encyclopedia of proteins and other biomolecules'' '''J. Struct Biol''' 175-244-52, [http://dx.doi.org/10.1016/j.jsb.2011.04.011 doi:10.1016/j.jsb.2011.04.011].

User talk:Lee Lip Pin

2011-12-04T03:14:19Z

Eran Hodis: Welcome!

'''Welcome to ''Proteopedia''!''' We hope you will contribute much and well. You will probably want to watch the narrated [[Proteopedia:Video_Guide|video guide]] and use the [[Help:Contents|help pages]] for later reference. Again, welcome and have fun! [[User:Eran Hodis|Eran Hodis]] 05:14, 4 December 2011 (IST)

User:Lee Lip Pin

2011-12-04T03:14:18Z

Eran Hodis: Creating user page with biography of new user.

*1]. Full Name : Rodney Lee Lip Pin
*2]. Position : Bio-Tech Entrepreneur [3]. Institution : Ying-Xiong-Mao Agency
*4]. Field of study : Electrical Engineering & Electrophysiology.

An enthusiast of symbolic logic and alchemy.

User talk:Torres Felix

2011-12-04T03:13:48Z

Eran Hodis: Welcome!

User:Torres Felix

2011-12-04T03:13:48Z

Eran Hodis: Creating user page with biography of new user.

*student in Paris descartes university.
*2nd year of pharmaceutical studies.

User talk:Ndeye Coumba

2011-11-27T23:55:54Z

Eran Hodis: Welcome!

User:Ndeye Coumba

2011-11-27T23:55:54Z

Eran Hodis: Creating user page with biography of new user.

Je suis étudiante en 1ere année de cycle ingénieur en biotechnologie à l'Ecole Supérieure de Biotechnologie de Strasbourg (ESBS), une école trinationale, unique en son genre, tournée vers l'enseignement des sciences de la vie sous toutes leurs formes.

(Undergraduate student studying biotechnology at ESBS in Strasbourg, France)

User talk:Nathalie Faggianelli

2011-11-27T23:55:08Z

Eran Hodis: Welcome!

User:Nathalie Faggianelli

2011-11-27T23:55:08Z

Eran Hodis: Creating user page with biography of new user.

Student in first year at the ESBS = Ecole Superieure de Biotechnologies de Strasbourg (France).

User talk:Celina Pinto

2011-11-25T18:32:36Z

Eran Hodis: Welcome!

User:Celina Pinto

2011-11-25T18:32:36Z

Eran Hodis: Creating user page with biography of new user.

I'm a Bachelor Student in Biotechnology at the ESBS (Ecole Supérieure de Biotechnologie de Strasbourg).

User talk:Camille Oms

2011-11-25T18:32:23Z

Eran Hodis: Welcome!

User:Camille Oms

2011-11-25T18:32:23Z

Eran Hodis: Creating user page with biography of new user.

I am a student in first year of ESBS, a biotechnology engineering school in Strasbourg.

User talk:Yoann Styczen

2011-11-25T18:31:38Z

Eran Hodis: Welcome!

User:Yoann Styczen

2011-11-25T18:31:38Z

Eran Hodis: Creating user page with biography of new user.

*DUT Génie biologique
*First year student in ESBS (Strasbourg)

User talk:Gourinchas Geoffrey

2011-11-25T18:30:40Z

Eran Hodis: Welcome!

User:Gourinchas Geoffrey

2011-11-25T18:30:40Z

Eran Hodis: Creating user page with biography of new user.

Student in first year of Biotechnologie ingenier in ESBS. (Ecole supérieure de Biotechnologie de Strasbourg)

User talk:Raphael Bilger

2011-11-25T18:30:26Z

Eran Hodis: Welcome!

User:Raphael Bilger

2011-11-25T18:30:26Z

Eran Hodis: Creating user page with biography of new user.

Hello, my name is Raphael Bilger and I am a student at the ESBS (Ecole Supérieure de Biotechnologies de Strasbourg) in France. Bruno Kieffer want us to create an article about a chosen protein. He reserved for my group the Sandbox 204.

User talk:Pascaline Menou

2011-11-25T18:29:57Z

Eran Hodis: Welcome!

User:Pascaline Menou

2011-11-25T18:29:57Z

Eran Hodis: Creating user page with biography of new user.

I am a first year student of the ESBS (Ecole Supérieure de Biotechnology de Strasbourg).

User talk:Brittany deRonde

2011-11-25T18:29:34Z

Eran Hodis: Welcome!

User:Brittany deRonde

2011-11-25T18:29:34Z

Eran Hodis: Creating user page with biography of new user.

I am a graduate student in the Department of Polymer Science and Engineering at the University of Massachusetts. I work for Professor Greg Tew.

User talk:Bleu Melusine

2011-11-25T18:28:55Z

Eran Hodis: Welcome!

User:Bleu Melusine

2011-11-25T18:28:55Z

Eran Hodis: Creating user page with biography of new user.

A french Student in Biotechnology in the ESBS (University of Strasbourg)

User talk:Virginie Grosboillot

2011-11-25T18:28:00Z

Eran Hodis: Welcome!

User:Virginie Grosboillot

2011-11-25T18:28:00Z

Eran Hodis: Creating user page with biography of new user.

Student at l'Ecole Supérieure de Biotechnologie de Strasbourg (ESBS)

User talk:Nicholas O'Connor

2011-11-20T15:19:12Z

Eran Hodis: Welcome!

User:Nicholas O'Connor

2011-11-20T15:19:12Z

Eran Hodis: Creating user page with biography of new user.

I am a 4th year undergraduate Bio student at UCSB. I am currently enrolled in a protein structure analysis lab requiring an in depth presentation on the protein of my choice. I also enjoy music, dancing, and video games!

User talk:Louise Cranfield

2011-11-20T15:19:00Z

Eran Hodis: Welcome!