2F5J

Crystal structure of MRG domain from human MRG15

Summary for 2F5J

• Entry DOI: 10.2210/pdb2f5j/pdb
• Related: 2F5K 2F5L
• Descriptor: Mortality factor 4-like protein 1 (2 entities in total)
• Functional Keywords: mrg fold, mainly a-helix, gene regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9UBU8
• Total number of polymer chains: 2
• Total formula weight: 42286.47

Authors

Zhang, P.,Du, J.,Ding, J. (deposition date: 2005-11-26, release date: 2006-11-14, Last modification date: 2024-03-13)

Primary citation

Zhang, P.,Zhao, J.,Wang, B.,Du, J.,Lu, Y.,Chen, J.,Ding, J.
The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14
Protein Sci., 15:2423-2434, 2006

PubMed Abstract: 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.

PubMed: 17008723
DOI: 10.1110/ps.062397806

Experimental method

X-RAY DIFFRACTION (2.2 Å)