5VEY

Solution NMR structure of histone H2A-H2B mono-ubiquitylated at H2A Lys15 in complex with RNF169 (653-708)

Summary for 5VEY

• Entry DOI: 10.2210/pdb5vey/pdb
• NMR Information: BMRB: 30275
• Descriptor: Histone H2B type 1-J,Histone H2A type 1-B/E, Polyubiquitin-B, E3 ubiquitin-protein ligase RNF169 (3 entities in total)
• Functional Keywords: nucleosome, ubiquitin, ubiquitin ligase, complex, transferase, structural protein, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 37252.71

Authors

Hu, Q.,Botuyan, M.V.,Cui, G.,Mer, G. (deposition date: 2017-04-06, release date: 2017-05-17, Last modification date: 2024-10-09)

Primary citation

Hu, Q.,Botuyan, M.V.,Cui, G.,Zhao, D.,Mer, G.
Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin Recruitment by RNF168/169 and RAD18.
Mol. Cell, 66:473-487.e9, 2017

PubMed Abstract: The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex. This conformational selection mechanism contrasts with the low-affinity binding mode of 53BP1, and it ensures 53BP1 displacement by RNF169 from NCP-ubme. We also show that RAD18 binds tightly to NCP-ubme through a ubiquitin-binding domain that contacts ubiquitin and nucleosome surfaces accessed by 53BP1. Our work uncovers diverse ubiquitin recognition mechanisms in the nucleosome, explaining how RNF168, RNF169, and RAD18 regulate 53BP1 chromatin recruitment and how specificity can be achieved in the recognition of a ubiquitin-modified substrate.

PubMed: 28506460
DOI: 10.1016/j.molcel.2017.04.009

Experimental method

SOLUTION NMR