Conserved Structural Mechanism of Specific Recognition of the Histone Variant H2A.Z by the YL1 Subunit of SRCAP Chromatin-remodeling Complex

The SRCAP complex regulates gene transcription through chromatin remodeling, where the subunit YL1 mediates the exchange of H2A-H2B dimers with H2A.Z-H2B in the nucleosome. We determined the high-resolution (2.01 Å) crystal structure of the N-terminal region (12-73) of the human SRCAP subunit YL1 in complex with H2B-H2A.Z, this domain termed as YL1-Z. YL1-Z consists of an alpha helix and a longer loop, which bind to H2A.Z-H2B to form a complex. In the structure, residues Phe29, Tyr30, Tyr34, and Phe37 of the YL1-Z domain specifically recognizes the hydrophobic residues Gln87, Ile90, Ile100, and Ile104 of H2A.Z through hydrophobic interactions, forming a hydrophobic core. Additionally, residues Asp55, Asp58, and Asp60 of YL1-Z form electrostatic interactions with Arg34 and Lys37 on H2A.Z, stabilizing the complex structure. The particular recognition has been validated in vitro by MBP-pulldown and ITC experiments. Our data show YL1 employ a conserved structural mechanism for recognizing H2A.Z-H2B dimer.