9nfv: Difference between revisions

Latest revision as of 04:55, 13 August 2026

Human SRCAP-CFDP1-nucleosome complex in the poised state of the H2A.Z histone exchange reaction (composite structure)

Structural highlights

9nfv is a 17 chain structure with sequence from Homo sapiens and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.8Å
Ligands:	ADP, ATP, MG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SRCAP_HUMAN Floating-Harbor syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

SRCAP_HUMAN Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The conserved yeast SWR1 and human SRCAP chromatin remodeling complexes catalyze exchange of nucleosomal histone H2A for H2A.Z, but the underlying mechanism has remained obscure. Here, we show that histone exchange by SRCAP requires the transient activator CFDP1 and resolve nine cryo-electron microscopy structures of the SRCAP-CFDP1 holoenzyme that define the stepwise exchange mechanism. CFDP1 recognizes the conformation of the fully engaged SRCAP-nucleosome complex through interactions with multiple subunits-including direct contact with the ATPase domain-and induces conformational transitions that drive extensive DNA unwrapping, eviction of the H2A-H2B dimer, and insertion of the H2A.Z-H2B dimer, all without necessarily requiring hydrolysis of bound ATP. Collectively, these findings provide unprecedented insight into the mechanism of activator- and nucleotide-driven histone exchange from nucleosomal H2A to H2A.Z.

Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme.,Park G, Wu C, Louder RK Sci Adv. 2026 Jul 31;12(31):eaei7728. doi: 10.1126/sciadv.aei7728. Epub 2026 Jul , 31. PMID:42536744^[7]

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

References

↑ Johnston H, Kneer J, Chackalaparampil I, Yaciuk P, Chrivia J. Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. J Biol Chem. 1999 Jun 4;274(23):16370-6. doi: 10.1074/jbc.274.23.16370. PMID:10347196 doi:https://dx.doi.org/10.1074/jbc.274.23.16370
↑ Monroy MA, Ruhl DD, Xu X, Granner DK, Yaciuk P, Chrivia JC. Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. J Biol Chem. 2001 Nov 2;276(44):40721-6. Epub 2001 Aug 24. PMID:11522779 doi:https://dx.doi.org/10.1074/jbc.M103615200
↑ Monroy MA, Schott NM, Cox L, Chen JD, Ruh M, Chrivia JC. SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Mol Endocrinol. 2003 Dec;17(12):2519-28. Epub 2003 Sep 18. PMID:14500758 doi:https://dx.doi.org/10.1210/me.2003-0208
↑ Eissenberg JC, Wong M, Chrivia JC. Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol Cell Biol. 2005 Aug;25(15):6559-69. doi: 10.1128/MCB.25.15.6559-6569.2005. PMID:16024792 doi:https://dx.doi.org/10.1128/MCB.25.15.6559-6569.2005
↑ Ruhl DD, Jin J, Cai Y, Swanson S, Florens L, Washburn MP, Conaway RC, Conaway JW, Chrivia JC. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry. 2006 May 2;45(17):5671-7. PMID:16634648 doi:https://dx.doi.org/10.1021/bi060043d
↑ Wong MM, Cox LK, Chrivia JC. The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. J Biol Chem. 2007 Sep 7;282(36):26132-9. Epub 2007 Jul 8. PMID:17617668 doi:https://dx.doi.org/M703418200
↑ Park G, Wu C, Louder RK. Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme. Science advances. 2026 Jul 31. doi: 10.1126/sciadv.aei7728. PMID: 42536744.

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Johnston H, Kneer J, Chackalaparampil I, Yaciuk P, Chrivia J. Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. J Biol Chem. 1999 Jun 4;274(23):16370-6. doi: 10.1074/jbc.274.23.16370. PMID:10347196 doi:https://dx.doi.org/10.1074/jbc.274.23.16370

[2] Monroy MA, Ruhl DD, Xu X, Granner DK, Yaciuk P, Chrivia JC. Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. J Biol Chem. 2001 Nov 2;276(44):40721-6. Epub 2001 Aug 24. PMID:11522779 doi:https://dx.doi.org/10.1074/jbc.M103615200

[3] Monroy MA, Schott NM, Cox L, Chen JD, Ruh M, Chrivia JC. SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Mol Endocrinol. 2003 Dec;17(12):2519-28. Epub 2003 Sep 18. PMID:14500758 doi:https://dx.doi.org/10.1210/me.2003-0208

[4] Eissenberg JC, Wong M, Chrivia JC. Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol Cell Biol. 2005 Aug;25(15):6559-69. doi: 10.1128/MCB.25.15.6559-6569.2005. PMID:16024792 doi:https://dx.doi.org/10.1128/MCB.25.15.6559-6569.2005

[5] Ruhl DD, Jin J, Cai Y, Swanson S, Florens L, Washburn MP, Conaway RC, Conaway JW, Chrivia JC. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry. 2006 May 2;45(17):5671-7. PMID:16634648 doi:https://dx.doi.org/10.1021/bi060043d

[6] Wong MM, Cox LK, Chrivia JC. The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. J Biol Chem. 2007 Sep 7;282(36):26132-9. Epub 2007 Jul 8. PMID:17617668 doi:https://dx.doi.org/M703418200

[7] Park G, Wu C, Louder RK. Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme. Science advances. 2026 Jul 31. doi: 10.1126/sciadv.aei7728. PMID: 42536744.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9nfv is ON HOLD  until Paper Publication
+==Human SRCAP-CFDP1-nucleosome complex in the poised state of the H2A.Z histone exchange reaction (composite structure)==
+<StructureSection load='9nfv' size='340' side='right'caption='[[9nfv]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9nfv]] is a 17 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9NFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NFV FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9nfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nfv OCA], [https://pdbe.org/9nfv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nfv RCSB], [https://www.ebi.ac.uk/pdbsum/9nfv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nfv ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SRCAP_HUMAN SRCAP_HUMAN] Floating-Harbor syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/SRCAP_HUMAN SRCAP_HUMAN] Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription.<ref>PMID:10347196</ref> <ref>PMID:11522779</ref> <ref>PMID:14500758</ref> <ref>PMID:16024792</ref> <ref>PMID:16634648</ref> <ref>PMID:17617668</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The conserved yeast SWR1 and human SRCAP chromatin remodeling complexes catalyze exchange of nucleosomal histone H2A for H2A.Z, but the underlying mechanism has remained obscure. Here, we show that histone exchange by SRCAP requires the transient activator CFDP1 and resolve nine cryo-electron microscopy structures of the SRCAP-CFDP1 holoenzyme that define the stepwise exchange mechanism. CFDP1 recognizes the conformation of the fully engaged SRCAP-nucleosome complex through interactions with multiple subunits-including direct contact with the ATPase domain-and induces conformational transitions that drive extensive DNA unwrapping, eviction of the H2A-H2B dimer, and insertion of the H2A.Z-H2B dimer, all without necessarily requiring hydrolysis of bound ATP. Collectively, these findings provide unprecedented insight into the mechanism of activator- and nucleotide-driven histone exchange from nucleosomal H2A to H2A.Z.
-Authors:
+Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme.,Park G, Wu C, Louder RK Sci Adv. 2026 Jul 31;12(31):eaei7728. doi: 10.1126/sciadv.aei7728. Epub 2026 Jul , 31. PMID:42536744<ref>PMID:42536744</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9nfv" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Xenopus laevis]]
+[[Category: Louder RK]]
+[[Category: Park G]]

9nfv: Difference between revisions

Latest revision as of 04:55, 13 August 2026

Human SRCAP-CFDP1-nucleosome complex in the poised state of the H2A.Z histone exchange reaction (composite structure)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools