RRC ID 21507
Author Zhang Z, Chang L, Yang J, Conin N, Kulkarni K, Barford D.
Title The four canonical tpr subunits of human APC/C form related homo-dimeric structures and stack in parallel to form a TPR suprahelix.
Journal J. Mol. Biol.
Abstract 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 (Cdc23(Nterm)). Cdc23(Nterm) is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23(Nterm) 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.
Volume 425(22)
Pages 4236-48
Published 2013-11-15
DOI 10.1016/j.jmb.2013.04.004
PII S0022-2836(13)00233-7
PMID 23583778
PMC PMC3898896
MeSH Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome / chemistry* Anaphase-Promoting Complex-Cyclosome / ultrastructure Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / chemistry Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome / chemistry Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome / chemistry Cell Cycle Proteins / chemistry Humans Minichromosome Maintenance Proteins / chemistry Models, Molecular Molecular Sequence Data Protein Conformation Protein Interaction Domains and Motifs Protein Multimerization* Protein Subunits* Saccharomyces cerevisiae / chemistry Saccharomyces cerevisiae / metabolism Schizosaccharomyces / chemistry Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / chemistry Sequence Alignment
IF 4.894
Times Cited 10
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Yeast pTN-TH7