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{{STRUCTURE_4j81|  PDB=4j81  |  SCENE=  }}
==Crystal structure of beta'-COP/Insig-1 complex==
===Crystal structure of beta'-COP/Insig-1 complex===
<StructureSection load='4j81' size='340' side='right' caption='[[4j81]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
{{ABSTRACT_PUBMED_23481256}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[4j81]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J81 FirstGlance]. <br>
==Function==
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4j73|4j73]], [[4j77|4j77]], [[4j78|4j78]], [[4j79|4j79]], [[4j82|4j82]], [[4j84|4j84]], [[4j86|4j86]], [[4j87|4j87]], [[4j8b|4j8b]], [[4j8g|4j8g]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j81 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j81 RCSB], [http://www.ebi.ac.uk/pdbsum/4j81 PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/COPB2_YEAST COPB2_YEAST]] The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.<ref>PMID:17101773</ref>  [[http://www.uniprot.org/uniprot/INSI1_HUMAN INSI1_HUMAN]] Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.<ref>PMID:12202038</ref> <ref>PMID:12535518</ref> <ref>PMID:16168377</ref> <ref>PMID:16399501</ref> <ref>PMID:16606821</ref>   
[[http://www.uniprot.org/uniprot/COPB2_YEAST COPB2_YEAST]] The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.<ref>PMID:17101773</ref>  [[http://www.uniprot.org/uniprot/INSI1_HUMAN INSI1_HUMAN]] Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.<ref>PMID:12202038</ref> <ref>PMID:12535518</ref> <ref>PMID:16168377</ref> <ref>PMID:16399501</ref> <ref>PMID:16606821</ref>   
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer alpha-COP and beta'-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval. Numerous ER/Golgi proteins contain K(x)Kxx motifs, but the rules for their recognition are unclear. We present crystal structures of alpha-COP and beta'-COP bound to a series of naturally occurring retrieval motifs-encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences. Binding experiments show that alpha-COP and beta'-COP have generally the same specificity for KKxx and KxKxx, but only beta'-COP recognizes the RKxx signal. Dilysine motif recognition involves lysine side-chain interactions with two acidic patches. Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches. We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.


==About this Structure==
Rules for the recognition of dilysine retrieval motifs by coatomer.,Ma W, Goldberg J EMBO J. 2013 Mar 12. doi: 10.1038/emboj.2013.41. PMID:23481256<ref>PMID:23481256</ref>
[[4j81]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J81 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<references group="xtra"/><references/>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Goldberg, J.]]
[[Category: Goldberg, J]]
[[Category: Ma, W.]]
[[Category: Ma, W]]
[[Category: Beta propeller domain]]
[[Category: Beta propeller domain]]
[[Category: Copi]]
[[Category: Copi]]

Revision as of 14:07, 25 December 2014

Crystal structure of beta'-COP/Insig-1 complexCrystal structure of beta'-COP/Insig-1 complex

Structural highlights

4j81 is a 4 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, RCSB, PDBsum

Function

[COPB2_YEAST] The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.[1] [INSI1_HUMAN] Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.[2] [3] [4] [5] [6]

Publication Abstract from PubMed

Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer alpha-COP and beta'-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval. Numerous ER/Golgi proteins contain K(x)Kxx motifs, but the rules for their recognition are unclear. We present crystal structures of alpha-COP and beta'-COP bound to a series of naturally occurring retrieval motifs-encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences. Binding experiments show that alpha-COP and beta'-COP have generally the same specificity for KKxx and KxKxx, but only beta'-COP recognizes the RKxx signal. Dilysine motif recognition involves lysine side-chain interactions with two acidic patches. Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches. We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.

Rules for the recognition of dilysine retrieval motifs by coatomer.,Ma W, Goldberg J EMBO J. 2013 Mar 12. doi: 10.1038/emboj.2013.41. PMID:23481256[7]

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

References

  1. ↑ Gabriely G, Kama R, Gerst JE. Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast. Mol Cell Biol. 2007 Jan;27(2):526-40. Epub 2006 Nov 13. PMID:17101773 doi:MCB.00577-06
  2. ↑ Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002 Aug 23;110(4):489-500. PMID:12202038
  3. ↑ Sever N, Yang T, Brown MS, Goldstein JL, DeBose-Boyd RA. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mol Cell. 2003 Jan;11(1):25-33. PMID:12535518
  4. ↑ Song BL, Sever N, DeBose-Boyd RA. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol Cell. 2005 Sep 16;19(6):829-40. PMID:16168377 doi:10.1016/j.molcel.2005.08.009
  5. ↑ Gong Y, Lee JN, Lee PC, Goldstein JL, Brown MS, Ye J. Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake. Cell Metab. 2006 Jan;3(1):15-24. PMID:16399501 doi:10.1016/j.cmet.2005.11.014
  6. ↑ Gong Y, Lee JN, Brown MS, Goldstein JL, Ye J. Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6154-9. Epub 2006 Apr 10. PMID:16606821 doi:0601923103
  7. ↑ Ma W, Goldberg J. Rules for the recognition of dilysine retrieval motifs by coatomer. EMBO J. 2013 Mar 12. doi: 10.1038/emboj.2013.41. PMID:23481256 doi:http://dx.doi.org/10.1038/emboj.2013.41

4j81, resolution 1.75Å

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