At the n-terminal region of trim5 is the ring domain which contains a putative e3 ubiquitin ligase activity that is important for auto ubiquitination of trim5 and also restriction of hiv-1[84].
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Abstract
TRIM5 is a restriction factor that blocks retrovirus infection soon after the virion core enters the cell cytoplasm. Restriction activity is targeted to the virion core via recognition of the capsid protein lattice that encases the viral genomic RNA. In common with all of the many TRIM family members, TRIM5 has RING, B-box, and coiled-coil domains. As an E3 ubiquitin ligase TRIM5 cooperates with the heterodimeric E2, UBC13/UEV1A, to activate the TAK1 (MAP3K7) kinase, NF-κB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines. TAK1, UBC13, and UEV1A all contribute to TRIM5-mediated retrovirus restriction activity. Interaction of the carboxy-terminal PRYSPRY or cyclophilin domains of TRIM5 with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. Structural and biochemical studies on TRIM5 have opened a much needed window on how the innate immune system detects the distinct molecular features of HIV-1 and other retroviruses.
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The tripartite motif (TRIM) family of proteins
TRIMs are multi-domain proteins defined by an N-terminal RING finger domain, one or two B-box domains, and a coiled-coil domain (Figure 1A). A large proportion of the TRIM proteins possess a C-terminal PRYSPRY domain that interacts with target proteins. Nearly 100 human genes encode TRIM proteins, and many of these are synthesized as multiple isoforms [1–3]. This enormous family of cellular proteins are involved in diverse cellular processes, including cell proliferation, differentiation, development, apoptosis, oncogenesis, and innate immunity. Of the many TRIM genes, several exhibit anti-retroviral activity, including TRIM11, 15, and 31 [4], TRIM1 [5,6], TRIM28 [7] and TRIM22 [8,9,9]. Among TRIM family members that inhibit HIV-1, TRIM5 is the best-studied.