8ims

From Proteopedia

Crystal structure of TRAF7 coiled-coil domain

Structural highlights

8ims is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TRAF7_HUMAN Meningioma;TRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

TRAF7_HUMAN E3 ubiquitin and SUMO-protein ligase that plays a role in different biological processes such as innate immunity, inflammation or apoptosis (PubMed:15001576, PubMed:37086853). Potentiates MAP3K3-mediated activation of JUN/AP1 and DDIT3 transcriptional regulators (PubMed:14743216). Negatively regulates MYB transcriptional activity by sequestering it to the cytosol via SUMOylation (By similarity). Plays a role in the phosphorylation of MAPK1 and/or MAPK3, probably via its interaction with MAP3K3. Negatively regulates RLR-mediated innate immunity by promoting 'Lys-48'-linked ubiquitination of TBK1 through its RING domain to inhibit the cellular antiviral response (PubMed:37086853). Promotes 'Lys-29'-linked polyubiquitination of NEMO/IKBKG and RELA leading to targeting these two proteins to lysosomal degradative pathways, reducing the transcriptional activity of NF-kappa-B (PubMed:21518757).[UniProtKB:Q922B6]^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear. In this study, we employed zebrafish as an in vivo model system. TRAF7 knock down caused defects in zebrafish embryonic development. We determined the crystal structure of TRAF7 CC domain at 3.3 A resolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development. Additionally, disease-causing mutations in TRAF7 CC region could impair the trimer formation, consequently impacting early embryonic development of zebrafish. Therefore, our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development.,Song X, Hu R, Chen Y, Xiao M, Zhang H, Wu S, Lu Q J Mol Cell Biol. 2024 Jul 1;16(1):mjad083. doi: 10.1093/jmcb/mjad083. PMID:38178633^[6]

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

References

↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004 Feb;6(2):97-105. Epub 2004 Jan 25. PMID:14743216 doi:http://dx.doi.org/10.1038/ncb1086
↑ Xu LG, Li LY, Shu HB. TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. J Biol Chem. 2004 Apr 23;279(17):17278-82. PMID:15001576 doi:10.1074/jbc.C400063200
↑ Zotti T, Uva A, Ferravante A, Vessichelli M, Scudiero I, Ceccarelli M, Vito P, Stilo R. TRAF7 protein promotes Lys-29-linked polyubiquitination of IkappaB kinase (IKKgamma)/NF-kappaB essential modulator (NEMO) and p65/RelA protein and represses NF-kappaB activation. J Biol Chem. 2011 Jul 1;286(26):22924-33. PMID:21518757 doi:10.1074/jbc.M110.215426
↑ Tokita MJ, Chen CA, Chitayat D, Macnamara E, Rosenfeld JA, Hanchard N, Lewis AM, Brown CW, Marom R, Shao Y, Novacic D, Wolfe L, Wahl C, Tifft CJ, Toro C, Bernstein JA, Hale CL, Silver J, Hudgins L, Ananth A, Hanson-Kahn A, Shuster S, Magoulas PL, Patel VN, Zhu W, Chen SM, Jiang Y, Liu P, Eng CM, Batkovskyte D, di Ronza A, Sardiello M, Lee BH, Schaaf CP, Yang Y, Wang X. De Novo Missense Variants in TRAF7 Cause Developmental Delay, Congenital Anomalies, and Dysmorphic Features. Am J Hum Genet. 2018 Jul 5;103(1):154-162. PMID:29961569 doi:10.1016/j.ajhg.2018.06.005
↑ Huang JP, Yang YX, Chen T, Wang DD, Li J, Xu LG. TRAF7 negatively regulates the RLR signaling pathway by facilitating the K48-linked ubiquitination of TBK1. Virol Sin. 2023 Jun;38(3):419-428. PMID:37086853 doi:10.1016/j.virs.2023.04.005
↑ Song X, Hu R, Chen Y, Xiao M, Zhang H, Wu S, Lu Q. The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development. J Mol Cell Biol. 2024 Jan 4:mjad083. PMID:38178633 doi:10.1093/jmcb/mjad083