9py7: Difference between revisions

Latest revision as of 05:24, 24 December 2025

Hamster Scap L1-L7 domain/Fab4G10 focused map

Structural highlights

9py7 is a 3 chain structure with sequence from Cricetulus griseus and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.8Å
Ligands:	NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SCAP_CRIGR Escort protein required for cholesterol as well as lipid homeostasis (PubMed:10497220, PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:8898195). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:10497220, PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:27068746, PubMed:8898195). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:27068746). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:27068746). Binds cholesterol via its SSD domain (PubMed:15260976, PubMed:27068746).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

References

↑ Rawson RB, DeBose-Boyd R, Goldstein JL, Brown MS. Failure to cleave sterol regulatory element-binding proteins (SREBPs) causes cholesterol auxotrophy in Chinese hamster ovary cells with genetic absence of SREBP cleavage-activating protein. J Biol Chem. 1999 Oct 1;274(40):28549-56. PMID:10497220 doi:10.1074/jbc.274.40.28549
↑ Yabe D, Xia ZP, Adams CM, Rawson RB. Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16672-7. PMID:12482938 doi:10.1073/pnas.262669399
↑ Radhakrishnan A, Sun LP, Kwon HJ, Brown MS, Goldstein JL. Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Mol Cell. 2004 Jul 23;15(2):259-68. PMID:15260976 doi:10.1016/j.molcel.2004.06.019
↑ Feramisco JD, Radhakrishnan A, Ikeda Y, Reitz J, Brown MS, Goldstein JL. Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3242-7. PMID:15728349 doi:10.1073/pnas.0500206102
↑ Sun LP, Li L, Goldstein JL, Brown MS. Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. J Biol Chem. 2005 Jul 15;280(28):26483-90. PMID:15899885 doi:10.1074/jbc.M504041200
↑ Sun LP, Seemann J, Goldstein JL, Brown MS. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6519-26. PMID:17428919 doi:10.1073/pnas.0700907104
↑ Zhang Y, Lee KM, Kinch LN, Clark L, Grishin NV, Rosenbaum DM, Brown MS, Goldstein JL, Radhakrishnan A. Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS. J Biol Chem. 2016 Jun 10;291(24):12888-12896. PMID:27068746 doi:10.1074/jbc.M116.729798
↑ Hua X, Nohturfft A, Goldstein JL, Brown MS. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell. 1996 Nov 1;87(3):415-26. PMID:8898195 doi:10.1016/s0092-8674(00)81362-8

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Rawson RB, DeBose-Boyd R, Goldstein JL, Brown MS. Failure to cleave sterol regulatory element-binding proteins (SREBPs) causes cholesterol auxotrophy in Chinese hamster ovary cells with genetic absence of SREBP cleavage-activating protein. J Biol Chem. 1999 Oct 1;274(40):28549-56. PMID:10497220 doi:10.1074/jbc.274.40.28549

[2] Yabe D, Xia ZP, Adams CM, Rawson RB. Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16672-7. PMID:12482938 doi:10.1073/pnas.262669399

[3] Radhakrishnan A, Sun LP, Kwon HJ, Brown MS, Goldstein JL. Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Mol Cell. 2004 Jul 23;15(2):259-68. PMID:15260976 doi:10.1016/j.molcel.2004.06.019

[4] Feramisco JD, Radhakrishnan A, Ikeda Y, Reitz J, Brown MS, Goldstein JL. Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3242-7. PMID:15728349 doi:10.1073/pnas.0500206102

[5] Sun LP, Li L, Goldstein JL, Brown MS. Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. J Biol Chem. 2005 Jul 15;280(28):26483-90. PMID:15899885 doi:10.1074/jbc.M504041200

[6] Sun LP, Seemann J, Goldstein JL, Brown MS. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6519-26. PMID:17428919 doi:10.1073/pnas.0700907104

[7] Zhang Y, Lee KM, Kinch LN, Clark L, Grishin NV, Rosenbaum DM, Brown MS, Goldstein JL, Radhakrishnan A. Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS. J Biol Chem. 2016 Jun 10;291(24):12888-12896. PMID:27068746 doi:10.1074/jbc.M116.729798

[8] Hua X, Nohturfft A, Goldstein JL, Brown MS. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell. 1996 Nov 1;87(3):415-26. PMID:8898195 doi:10.1016/s0092-8674(00)81362-8

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9py7 is ON HOLD  until 2027-08-07
+==Hamster Scap L1-L7 domain/Fab4G10 focused map==
+<StructureSection load='9py7' size='340' side='right'caption='[[9py7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9py7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PY7 FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9py7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9py7 OCA], [https://pdbe.org/9py7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9py7 RCSB], [https://www.ebi.ac.uk/pdbsum/9py7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9py7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SCAP_CRIGR SCAP_CRIGR] Escort protein required for cholesterol as well as lipid homeostasis (PubMed:10497220, PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:8898195). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:10497220, PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:27068746, PubMed:8898195). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (PubMed:12482938, PubMed:15728349, PubMed:15899885, PubMed:27068746). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (PubMed:15728349, PubMed:15899885, PubMed:17428919, PubMed:27068746). Binds cholesterol via its SSD domain (PubMed:15260976, PubMed:27068746).<ref>PMID:10497220</ref> <ref>PMID:12482938</ref> <ref>PMID:15260976</ref> <ref>PMID:15728349</ref> <ref>PMID:15899885</ref> <ref>PMID:17428919</ref> <ref>PMID:27068746</ref> <ref>PMID:8898195</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Cricetulus griseus]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Bai X]]
+[[Category: Kober DL]]
+[[Category: Radhakrishnan A]]
+[[Category: Rosenbaum DM]]
+[[Category: Williams BC]]

9py7: Difference between revisions

Latest revision as of 05:24, 24 December 2025

Hamster Scap L1-L7 domain/Fab4G10 focused map

Structural highlights

Function

References

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