Polycomb-group RING finger homologs (PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, and PCGF6) are critical components in the assembly of distinct Polycomb repression complex 1 (PRC1)-related complexes. Here, we identify a protein interaction domain in BCL6 corepressor, BCOR, which binds the RING finger- and WD40-associated ubiquitin-like (RAWUL) domain of PCGF1 (NSPC1) and PCGF3 but not of PCGF2 (MEL18) or PCGF4 (BMI1). Because of the selective binding, we have named this domain PCGF Ub-like fold discriminator (PUFD). The structure of BCOR PUFD bound to PCGF1 reveals that (1) PUFD binds to the same surfaces as observed for a different Polycomb group RAWUL domain and (2) the ability of PUFD to discriminate among RAWULs stems from the identity of specific residues within these interaction surfaces. These data show the molecular basis for determining the binding preference for a PCGF homolog, which ultimately helps determine the identity of the larger PRC1-like assembly.
Bibliographical noteFunding Information:
This work was supported by the American Heart Association (0830111N to C.A.K.), the American Cancer Society (RSG-08-285-01-GMC to C.A.K.), the Department of Defense Breast Cancer Research Program (BC075278 to C.A.K.), the National Institutes of Health (5R01CA071540 to V.J.B.), NIH-NCI (2P30 CA054174-17 to B.D. and P.J.H.), XSEDE (TG-MCB070039 to B.D.), and the Welch Foundation (AQ-1399 to P.J.H.). UTHSCSA core facilities are supported by the UTHSCSA Executive Research Committee and the Cancer Therapy Research Center. This work is based upon research at Beamline 4.2.2 of the Molecular Biology Consortium at the Advance Light Source (ALS). ALS is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Advanced Photon Source is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant 085P1000817). We also thank Dr. Jay Nix (ALS) and Dr. Dmitri Ivanov (APS) for assistance with the data collection.