Integrative Modeling of a Sin3/HDAC Complex Sub-structure

被引：30

作者：

Banks, Charles A. S. ^{[1
]}

Zhang, Ying ^{[1
]}

Miah, Sayem ^{[1
]}

Hao, Yan ^{[1
]}

Adams, Mark K. ^{[1
]}

Wen, Zhihui ^{[1
]}

Thornton, Janet L. ^{[1
]}

Florens, Laurence ^{[1
]}

Washburn, Michael P. ^{[1
,2
]}

机构：

[1] Stowers Inst Med Res, Kansas City, MO 64110 USA

[2] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA

来源：

CELL REPORTS | 2020年 / 31卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MASS-SPECTROMETRY; CROSS-LINKING; DISTANCE RESTRAINTS; WEB SERVER; COREPRESSOR; IDENTIFICATION; TRANSCRIPTION; RECOGNITION; TECHNOLOGY; INHIBITOR;

D O I：

10.1016/j.celrep.2020.03.080

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Sin3/HDAC complexes function by deacetylating histones, condensing chromatin, and modulating gene expression. Although components used to build these complexes have been well defined, we still have only a limited understanding of the structure of the Sin3/HDAC subunits assembled around the scaffolding protein SIN3A. To characterize the spatial arrangement of Sin3 subunits, we combined Halo affinity capture, chemical crosslinking, and high-resolution mass spectrometry (XL-MS) to determine intersubunit distance constraints, identifying 66 interprotein and 63 self-crosslinks for 13 Sin3 subunits. Having assessed crosslink authenticity by mapping self-crosslinks onto existing structures, we used distance restraints from interprotein crosslinks to guide assembly of a Sin3 complex substructure. We identified the relative positions of subunits SAP30L, HDAC1, SUDS3, HDAC2, and ING1 around the SIN3A scaffold. The architecture of this subassembly suggests that multiple factors have space to assemble to collectively influence the behavior of the catalytic subunit HDAC1.

引用

页数：14

共 48 条

[1] A Structured Workflow for Mapping Human Sin3 Histone Deacetylase Complex Interactions Using Halo-MudPIT Affinity-Purification Mass Spectrometry [J].