3zn3
From Proteopedia
N-terminal domain of S. pombe Cdc23 APC subunit
Structural highlights
Function[APC8_SCHPO] Component of the anaphase-promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C is thought to confer substrate specificity and, in the presence of ubiquitin-conjugating E2 enzymes, it catalyzes the formation of protein-ubiquitin conjugates that are subsequently degraded by the 26S proteasome. Has a role in promoting metaphase to anaphase transition via the ubiquitination of specific mitotic substrates.[1] Publication Abstract from PubMedThe anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for >80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23Nterm). Cdc23Nterm is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23Nterm structure, we generated a model of full-length Cdc23. The resultant "V"-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes. The Four Canonical TPR Subunits of Human APC/C Form Related Homo-Dimeric Structures and Stack in Parallel to Form a TPR Suprahelix.,Zhang Z, Chang L, Yang J, Conin N, Kulkarni K, Barford D J Mol Biol. 2013 Apr 11. pii: S0022-2836(13)00233-7. doi:, 10.1016/j.jmb.2013.04.004. PMID:23583778[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Cbs 356 | Barford, D | Conin, N | Kulkarni, K | Yang, J | Zhang, Z | Cell cycle | Tpr
