2f5j

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2f5j, resolution 2.20Å

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Crystal structure of MRG domain from human MRG15

Overview

MRG15 is a transcription factor expressed in a variety of human tissues, and its orthologs have been found in many other eukaryotes which, constitute the MRG protein family. It plays a vital role in embryonic, development and cell proliferation, and is involved in cellular, senescence. The C-terminal part of MRG15 forms a conserved MRG domain, which is involved in interactions with the tumor suppressor protein, retinoblastoma and a nucleoprotein PAM14 during transcriptional, regulation. We report here the characterization of the interaction between, the MRG domain of human MRG15 and PAM14 using both yeast two-hybrid and in, vitro binding assays based on the crystal structure of the MRG domain. The, MRG domain is predominantly hydrophobic, and consists of mainly, alpha-helices that are arranged in a three-layer sandwich topology. The, hydrophobic core is stabilized by interactions among a number of conserved, hydrophobic residues. The molecular surface is largely hydrophobic, but, contains a few hydrophilic patches. Structure-based site-directed, mutagenesis studies identified key residues involved in the binding of, PAM14. Structural and biochemical data together demonstrate that the PAM14, binding site is consisted of residues Ile160, Leu168, Val169, Trp172, Tyr235, Val268, and Arg269 of MRG15, which form a shallow hydrophobic, pocket to interact with the N-terminal 50 residues of PAM14 through, primarily hydrophobic interactions. These results provide the molecular, basis for the interaction between the MRG domain and PAM14, and reveal, insights into the potential biological function of MRG15 in transcription, regulation and chromatin remodeling.

About this Structure

2F5J is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14., Zhang P, Zhao J, Wang B, Du J, Lu Y, Chen J, Ding J, Protein Sci. 2006 Oct;15(10):2423-34. PMID:17008723

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