7qrx | pdb_00007qrx
Crystal structure of NHL domain of TRIM71
Structural highlights
DiseaseLIN41_HUMAN Congenital communicating hydrocephalus. The disease is caused by variants affecting the gene represented in this entry. FunctionLIN41_HUMAN E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance (Probable). Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A (By similarity). In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism (PubMed:23125361). Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1 (By similarity). Specific regulator of miRNA biogenesis. Binds to miRNA MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression (PubMed:28431233).[UniProtKB:Q1PSW8][1] [2] [3] Publication Abstract from PubMedTripartite 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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