8CWW

Structure of S. cerevisiae Hop1 CBR bound to a nucleosome

Summary for 8CWW

• Entry DOI: 10.2210/pdb8cww/pdb
• EMDB information: 27030
• Descriptor: Meiosis-specific protein HOP1, Histone H3, Histone H4, ... (8 entities in total)
• Functional Keywords: meiosis, recombination, chromosome axis, nucleosome, phd, winged helix, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 11
• Total formula weight: 222642.46

Authors

Gu, Y.,Ur, S.N.,Milano, C.R.,Tromer, E.C.,Vale-Silva, L.A.,Hochwagen, A.,Corbett, K.D. (deposition date: 2022-05-19, release date: 2023-06-07, Last modification date: 2024-04-10)

Primary citation

Milano, C.R.,Ur, S.N.,Gu, Y.,Zhang, J.,Allison, R.,Brown, G.,Neale, M.J.,Tromer, E.C.,Corbett, K.D.,Hochwagen, A.
Chromatin binding by HORMAD proteins regulates meiotic recombination initiation.
Embo J., 43:836-867, 2024

PubMed Abstract: The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. In S. cerevisiae, the HORMAD protein Hop1 mediates the enrichment of axis proteins at nucleosome-rich islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix-turn-helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes a localized reduction of axis protein binding and meiotic DNA double-strand breaks (DSBs) in axis islands and leads to defects in chromosome synapsis. Synthetic effects with mutants of the Hop1 regulator Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of the CBR, suggesting that the mechanisms we uncover are broadly conserved.

PubMed: 38332377
DOI: 10.1038/s44318-024-00034-3

Experimental method

ELECTRON MICROSCOPY (2.74 Å)