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From Proteopedia
Crystal structure of TRIM7 B30.2 domain at 1.8 angstrom resolution
Structural highlights
FunctionTRIM7_HUMAN E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7][1] [2] (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.[3] Publication Abstract from PubMedTRIM7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1, 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 tripartite motif (TRIM) and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C-terminus. In order 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(B30.2)) in two crystal forms at resolutions of 1.6 A and 1.8 A. TRIM7(B30.2) exhibits the typical B30.2 domain fold, consisting of two antiparallel beta-sheets of seven and six strands, arranged as a distorted beta-sandwich. Furthermore, two long loops partially cover the concave face of the beta-sandwich defined by the beta-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 glycogenin-1. These studies showed that Leu423, Ser499 and Cys501 of TRIM7(B30.2), and the C-terminal 33 amino acids of glycogenin-1 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(B30.2)-glycogenin-1 C-terminal peptide complex. These data provide useful information that can be used to target this interaction for the development of potential therapeutic agents. Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1.,Munoz Sosa CJ, Issoglio FM, Carrizo ME J Biol Chem. 2021 May 11:100772. doi: 10.1016/j.jbc.2021.100772. PMID:33989636[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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