6UMA

Crystal structure of the TRIM7 B30.2 domain at 1.6 angstrom resolution

Summary for 6UMA

• Entry DOI: 10.2210/pdb6uma/pdb
• Related: 6UMB
• Descriptor: E3 ubiquitin-protein ligase TRIM7, MALONATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: b30.2, e3 ubiquitin ligase, pry/spry, trim7, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 41140.50

Authors

Munoz Sosa, C.J.,Carrizo, M.E. (deposition date: 2019-10-09, release date: 2021-04-14, Last modification date: 2024-11-06)

Primary citation

Munoz Sosa, C.J.,Issoglio, F.M.,Carrizo, M.E.
Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1.
J.Biol.Chem., 296:100772-100772, 2021

PubMed Abstract: Tripartite motif (TRIM)7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1 (GN1), the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis and, thus, represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal TRIM and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C terminus. To contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7) in two crystal forms at resolutions of 1.6 Å and 1.8 Å. TRIM7 exhibits the typical B30.2 domain fold, consisting of two antiparallel β-sheets of seven and six strands, arranged as a distorted β-sandwich. Furthermore, two long loops partially cover the concave face of the β-sandwich defined by the β-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for GN1. These studies showed that Leu423, Ser499, and Cys501 of TRIM7 and the C-terminal 33 amino acids of GN1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7-GN1 C-terminal peptide complex. These data provide useful information that could be used to target this interaction for the development of potential therapeutic agents.

PubMed: 33989636
DOI: 10.1016/j.jbc.2021.100772

Experimental method

X-RAY DIFFRACTION (1.6 Å)