Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

Author:

Worden Evan J1ORCID,Zhang Xiangbin1,Wolberger Cynthia1ORCID

Affiliation:

1. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States

Abstract

Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxxxRR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.

Funder

National Institute of General Medical Sciences

Damon Runyon Cancer Research Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference63 articles.

1. PHENIX : a comprehensive Python-based system for macromolecular structure solution;Adams;Acta Crystallographica Section D Biological Crystallography,2010

2. Real-space refinement in PHENIX for cryo-EM and crystallography;Afonine;Acta Crystallographica Section D Structural Biology,2018

3. Structural basis for recognition of ubiquitylated nucleosome by Dot1L methyltransferase;Anderson;Cell Reports,2019

4. Nucleosome structure(s) and stability: variations on a theme;Andrews;Annual Review of Biophysics,2011

5. Structural and biochemical insights into MLL1 core complex assembly;Avdic;Structure,2011

Cited by 83 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3