5bxb | pdb_00005bxb
Crystal structure of pentameric KCTD1 BTB domain form 1
Structural highlights
DiseaseKCTD1_HUMAN Scalp-ear-nipple syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionKCTD1_HUMAN May repress the transcriptional activity of AP-2 family members, including TFAP2A, TFAP2B and TFAP2C to various extent.[1] [2] Publication Abstract from PubMedCullin3 (Cul3)-based ubiquitin E3 ligase complexes catalyze the transfer of ubiquitin from an E2 enzyme to target substrate proteins. In these assemblies, the C-terminal region of Cul3 binds Rbx1/E2~ubiquitin, while the N-terminal region interacts with various BTB domain proteins that serve as substrate adaptors. Previous crystal structures of the homodimeric BTB proteins KLHL3, KLHL11 and SPOP in complex with the N-terminal domain of Cul3 revealed the features required for Cul3 recognition in these proteins. A second class of BTB-domain containing proteins, the KCTD proteins, are also Cul3 substrate adaptors, but these do not share many of the previously identified determinants for Cul3 binding. We report the pentameric crystal structures of the KCTD1 and KCTD9 BTB domains, and identify plasticity in the KCTD1 rings. We find that the KCTD proteins 5, 6, 9, and 17 bind to Cul3 with high affinity, while the KCTD proteins 1 and 16 do not have detectable binding. Finally, we confirm the 5:5 assembly of KCTD9/Cul3 complexes by electron cryomicroscopy and provide a molecular rationale for BTB-mediated Cul3 binding specificity in the KCTD family. Structural insights into KCTD protein assembly and Cullin3 recognition.,Ji AX, Chu A, Nielsen TK, Benlekbir S, Rubinstein JL, Prive GG J Mol Biol. 2015 Aug 31. pii: S0022-2836(15)00484-2. doi:, 10.1016/j.jmb.2015.08.019. PMID:26334369[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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