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Publication Abstract from PubMed

Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of the RING-type E3 ubiquitin ligases that play a role in diverse processes from homeostasis and immune response to viral restriction. While TRIM proteins typically harbor an N-terminal RING finger, a B-box and a coiled-coil domain, a high degree of diversity lies in their C termini that contain diverse protein interaction modules, most of which, both structures and their roles in intermolecular interactions, remain unknown. Here, high-resolution crystal structures of the NHL domains of three of the four human TRIM-NHL proteins, namely TRIM2, TRIM3 and TRIM71, are presented. Comparative structural analyses revealed that, despite sharing an evolutionarily conserved six-bladed beta-propeller architecture, the low sequence identities resulted in distinct properties of these interaction domains at their putative binding sites for macromolecules. Interestingly, residues lining the binding cavities represent a hotspot for genetic mutations linked to several diseases. Thus, high sequence diversity within the conserved NHL domains might be essential for differentiating binding partners among TRIM-NHL proteins.

Comparative structural analyses of the NHL domains from the human E3 ligase TRIM-NHL family.,Chaikuad A, Zhubi R, Tredup C, Knapp S IUCrJ. 2022 Sep 27;9(Pt 6):720-727. doi: 10.1107/S2052252522008582. eCollection , 2022 Nov 1. PMID:36381143^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.