6vpr: Difference between revisions

Latest revision as of 09:58, 25 December 2024

Crystal structure of the C-terminal domain of DENR

Structural highlights

6vpr is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	ACT, HG, PO4, SO4, TLA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DENR_HUMAN May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The density regulated protein (DENR) forms a stable heterodimer with malignant T-cell-amplified sequence 1 (MCT-1). DENR-MCT-1 heterodimer then participates in regulation of non-canonical translation initiation and ribosomal recycling. The N-terminal domain of DENR interacts with MCT-1 and carries a classical tetrahedral zinc ion-binding site, which is crucial for the dimerization. DENR-MCT-1 binds the small (40S) ribosomal subunit through interactions between MCT-1 and helix h24 of the 18S rRNA, and through interactions between the C-terminal domain of DENR and helix h44 of the 18S rRNA. This later interaction occurs in the vicinity of the P site that is also the binding site for canonical translation initiation factor eIF1, which plays the key role in initiation codon selection and scanning. Sequence homology modeling and a low-resolution crystal structure of the DENR-MCT-1 complex with the human 40S subunit suggests that the C-terminal domain of DENR and eIF1 adopt a similar fold. Here we present the crystal structure of the C-terminal domain of DENR determined at 1.74 A resolution, which confirms its resemblance to eIF1 and advances our understanding of the mechanism by which DENR-MCT-1 regulates non-canonical translation initiation and ribosomal recycling.

Crystal structure of the C-terminal domain of DENR.,Lomakin IB, De S, Wang J, Borkar AN, Steitz TA Comput Struct Biotechnol J. 2020 Mar 19;18:696-704. doi:, 10.1016/j.csbj.2020.03.009. eCollection 2020. PMID:32257053^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer Res. 2006 Sep 15;66(18):8994-9001. PMID:16982740 doi:66/18/8994
↑ Mazan-Mamczarz K, Gartenhaus RB. Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1. Cancer Genomics Proteomics. 2007 May-Jun;4(3):233-9. PMID:17878526
↑ Skabkin MA, Skabkina OV, Dhote V, Komar AA, Hellen CU, Pestova TV. Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling. Genes Dev. 2010 Aug 15;24(16):1787-801. doi: 10.1101/gad.1957510. PMID:20713520 doi:https://dx.doi.org/10.1101/gad.1957510
↑ Lomakin IB, De S, Wang J, Borkar AN, Steitz TA. Crystal structure of the C-terminal domain of DENR. Comput Struct Biotechnol J. 2020 Mar 19;18:696-704. doi:, 10.1016/j.csbj.2020.03.009. eCollection 2020. PMID:32257053 doi:https://dx.doi.org/10.1016/j.csbj.2020.03.009

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer Res. 2006 Sep 15;66(18):8994-9001. PMID:16982740 doi:66/18/8994

[2] Mazan-Mamczarz K, Gartenhaus RB. Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1. Cancer Genomics Proteomics. 2007 May-Jun;4(3):233-9. PMID:17878526

[3] Skabkin MA, Skabkina OV, Dhote V, Komar AA, Hellen CU, Pestova TV. Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling. Genes Dev. 2010 Aug 15;24(16):1787-801. doi: 10.1101/gad.1957510. PMID:20713520 doi:https://dx.doi.org/10.1101/gad.1957510

[4] Lomakin IB, De S, Wang J, Borkar AN, Steitz TA. Crystal structure of the C-terminal domain of DENR. Comput Struct Biotechnol J. 2020 Mar 19;18:696-704. doi:, 10.1016/j.csbj.2020.03.009. eCollection 2020. PMID:32257053 doi:https://dx.doi.org/10.1016/j.csbj.2020.03.009

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6vpr is ON HOLD
+==Crystal structure of the C-terminal domain of DENR==
+<StructureSection load='6vpr' size='340' side='right'caption='[[6vpr]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6vpr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VPR FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vpr OCA], [https://pdbe.org/6vpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vpr RCSB], [https://www.ebi.ac.uk/pdbsum/6vpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vpr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DENR_HUMAN DENR_HUMAN] May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.<ref>PMID:16982740</ref> <ref>PMID:17878526</ref> <ref>PMID:20713520</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The density regulated protein (DENR) forms a stable heterodimer with malignant T-cell-amplified sequence 1 (MCT-1). DENR-MCT-1 heterodimer then participates in regulation of non-canonical translation initiation and ribosomal recycling. The N-terminal domain of DENR interacts with MCT-1 and carries a classical tetrahedral zinc ion-binding site, which is crucial for the dimerization. DENR-MCT-1 binds the small (40S) ribosomal subunit through interactions between MCT-1 and helix h24 of the 18S rRNA, and through interactions between the C-terminal domain of DENR and helix h44 of the 18S rRNA. This later interaction occurs in the vicinity of the P site that is also the binding site for canonical translation initiation factor eIF1, which plays the key role in initiation codon selection and scanning. Sequence homology modeling and a low-resolution crystal structure of the DENR-MCT-1 complex with the human 40S subunit suggests that the C-terminal domain of DENR and eIF1 adopt a similar fold. Here we present the crystal structure of the C-terminal domain of DENR determined at 1.74 A resolution, which confirms its resemblance to eIF1 and advances our understanding of the mechanism by which DENR-MCT-1 regulates non-canonical translation initiation and ribosomal recycling.
-Authors: Lomakin, I.B., Steitz, T.A.
+Crystal structure of the C-terminal domain of DENR.,Lomakin IB, De S, Wang J, Borkar AN, Steitz TA Comput Struct Biotechnol J. 2020 Mar 19;18:696-704. doi:, 10.1016/j.csbj.2020.03.009. eCollection 2020. PMID:32257053<ref>PMID:32257053</ref>
-Description: Crystal structure of the C-terminal domain of DENR
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lomakin, I.B]]
+<div class="pdbe-citations 6vpr" style="background-color:#fffaf0;"></div>
-[[Category: Steitz, T.A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Lomakin IB]]
+[[Category: Steitz TA]]

6vpr: Difference between revisions

Latest revision as of 09:58, 25 December 2024

Crystal structure of the C-terminal domain of DENR

Structural highlights

Function

Publication Abstract from PubMed

References

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