7smc
From Proteopedia
p107 pocket domain complexed with ARID4A peptide
Structural highlights
FunctionRBL1_HUMAN Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with adenovirus E1A and with SV40 large T antigen. May bind and modulate functionally certain cellular proteins with which T and E1A compete for pocket binding. May act as a tumor suppressor. Publication Abstract from PubMedThe retinoblastoma protein (Rb) and its homologs p107 and p130 are critical regulators of gene expression during the cell cycle and are commonly inactivated in cancer. Rb proteins use their "pocket domain" to bind an LxCxE sequence motif in other proteins, many of which function with Rb proteins to co-regulate transcription. Here, we present binding data and crystal structures of the p107 pocket domain in complex with LxCxE peptides from the transcriptional co-repressor proteins HDAC1, ARID4A, and EID1. Our results explain why Rb and p107 have weaker affinity for cellular LxCxE proteins compared with the E7 protein from human papillomavirus, which has been used as the primary model for understanding LxCxE motif interactions. Our structural and mutagenesis data also identify and explain differences in Rb and p107 affinities for some LxCxE-containing sequences. Our study provides new insights into how Rb proteins bind their cell partners with varying affinity and specificity. Structural basis for tunable affinity and specificity of LxCxE-dependent protein interactions with the retinoblastoma protein family.,Putta S, Alvarez L, Ludtke S, Sehr P, Muller GA, Fernandez SM, Tripathi S, Lewis J, Gibson TJ, Chemes LB, Rubin SM Structure. 2022 Sep 1;30(9):1340-1353.e3. doi: 10.1016/j.str.2022.05.019. Epub, 2022 Jun 17. PMID:35716663[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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