論文 - 詳細
| RRC ID | 21507 |
|---|---|
| 著者 | Zhang Z, Chang L, Yang J, Conin N, Kulkarni K, Barford D. |
| タイトル | The four canonical tpr subunits of human APC/C form related homo-dimeric structures and stack in parallel to form a TPR suprahelix. |
| ジャーナル | J Mol Biol |
| Abstract |
The 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 (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. |
| 巻・号 | 425(22) |
| ページ | 4236-48 |
| 公開日 | 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 | 4.76 |
| 引用数 | 15 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | pTN-TH7 |