2e3s: Difference between revisions

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== Structural highlights ==

<table><tr><td colspan='2'>[[2e3s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3S FirstGlance]. <br>

<table><tr><td colspan='2'>[[2e3s]] is a 1 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=2E3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3S 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]] 1.94Å</td></tr>

~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~|~~Gene:~~]]~~</b></td><td class="sblockDat">CERT ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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=2e3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e3s OCA], [https://pdbe.org/2e3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e3s RCSB], [https://www.ebi.ac.uk/pdbsum/2e3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e3s ProSAT]</span></td></tr>

</table>

== Disease ==

[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] The disease is caused by variants affecting the gene represented in this entry.

== Function ==

[[https://www.uniprot.org/uniprot/~~C43BP_HUMAN C43BP_HUMAN]~~] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>

[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>

== Evolutionary Conservation ==

[[Image:Consurf_key_small.gif|200px|right]]

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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e3s ConSurf].

~~<div style="background-color:#fffaf0;">~~

~~== Publication Abstract from PubMed ==~~

In mammalian cells, ceramide is synthesized in the endoplasmic reticulum and transferred to the Golgi apparatus for conversion to sphingomyelin. Ceramide transport occurs in a nonvesicular manner and is mediated by CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain. The CERT START domain efficiently transfers natural D-erythro-C16-ceramide, but not lipids with longer (C20) amide-acyl chains. The molecular mechanisms of ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT START domain in its apo-form and in complex with ceramides having different acyl chain lengths. In these complex structures, one ceramide molecule is buried in a long amphiphilic cavity. At the far end of the cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond network with specific amino acid residues that play key roles in stereo-specific ceramide recognition. At the head of the ceramide molecule, there is no extra space to accommodate additional bulky groups. The two aliphatic chains of ceramide are surrounded by the hydrophobic wall of the cavity, whose size and shape dictate the length limit for cognate ceramides. Furthermore, local high-crystallographic B-factors suggest that the alpha-3 and the Omega1 loop might work as a gate to incorporate the ceramide into the cavity. Thus, the structures demonstrate the structural basis for the mechanism by which CERT can distinguish ceramide from other lipid types yet still recognize multiple species of ceramides.

Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide.,Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806<ref>PMID:18184806</ref>

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

~~</div>~~

~~<div class="pdbe-citations 2e3s" style="background-color:#fffaf0;"></div>~~

== References ==

__TOC__

</StructureSection>

[[Category: ~~Human~~]]

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Hanada, K]]

[[Category: Hanada K]]

[[Category: Kato, R]]

[[Category: Kato R]]

[[Category: Kudo, N]]

[[Category: Kudo N]]

[[Category: Kumagai, K]]

[[Category: Kumagai K]]

[[Category: Nishijima, M]]

[[Category: Nishijima M]]

[[Category: Wakatsuki, S]]

[[Category: Wakatsuki S]]

~~[[Category: Ceramide transfer]]~~

~~[[Category: Cert]]~~

~~[[Category: Lipid transfer protein]]~~

~~[[Category: Lipid transport~~]]

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@@ Line 3: / Line 3: @@
 <StructureSection load='2e3s' size='340' side='right'caption='[[2e3s]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2e3s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2e3s]] is a 1 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=2E3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3S FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2e3m|2e3m]], [[2e3n|2e3n]], [[2e3o|2e3o]], [[2e3p|2e3p]], [[2e3q|2e3q]], [[2e3r|2e3r]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CERT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2e3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e3s OCA], [https://pdbe.org/2e3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e3s RCSB], [https://www.ebi.ac.uk/pdbsum/2e3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e3s ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/C43BP_HUMAN C43BP_HUMAN]] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>
+[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 20: / Line 21: @@
 </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e3s ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-In mammalian cells, ceramide is synthesized in the endoplasmic reticulum and transferred to the Golgi apparatus for conversion to sphingomyelin. Ceramide transport occurs in a nonvesicular manner and is mediated by CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain. The CERT START domain efficiently transfers natural D-erythro-C16-ceramide, but not lipids with longer (C20) amide-acyl chains. The molecular mechanisms of ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT START domain in its apo-form and in complex with ceramides having different acyl chain lengths. In these complex structures, one ceramide molecule is buried in a long amphiphilic cavity. At the far end of the cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond network with specific amino acid residues that play key roles in stereo-specific ceramide recognition. At the head of the ceramide molecule, there is no extra space to accommodate additional bulky groups. The two aliphatic chains of ceramide are surrounded by the hydrophobic wall of the cavity, whose size and shape dictate the length limit for cognate ceramides. Furthermore, local high-crystallographic B-factors suggest that the alpha-3 and the Omega1 loop might work as a gate to incorporate the ceramide into the cavity. Thus, the structures demonstrate the structural basis for the mechanism by which CERT can distinguish ceramide from other lipid types yet still recognize multiple species of ceramides.
-Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide.,Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806<ref>PMID:18184806</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 2e3s" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hanada, K]]
+[[Category: Hanada K]]
-[[Category: Kato, R]]
+[[Category: Kato R]]
-[[Category: Kudo, N]]
+[[Category: Kudo N]]
-[[Category: Kumagai, K]]
+[[Category: Kumagai K]]
-[[Category: Nishijima, M]]
+[[Category: Nishijima M]]
-[[Category: Wakatsuki, S]]
+[[Category: Wakatsuki S]]
-[[Category: Ceramide transfer]]
-[[Category: Cert]]
-[[Category: Lipid transfer protein]]
-[[Category: Lipid transport]]