5u1t
From Proteopedia
Crystal structure of the Saccharomyces cerevisiae separase-securin complex at 2.6 angstrom resolution
Structural highlights
Function[ESP1_YEAST] Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the MCD1/SCC1 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by securin/PDS1 protein. It also promotes anaphase spindle elongation. A component of the FEAR (CDC14 early anaphase release) network which promotes CDC14 release from the nucleolus during early anaphase. Cleaves SLK19.[1] [2] [3] [4] [SECU_YEAST] Regulatory protein, which plays a central role in chromosome stability. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESP1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESP1.[5] Publication Abstract from PubMedSeparase is a cysteine protease with a crucial role in the dissolution of cohesion among sister chromatids during chromosome segregation. In human tumours separase is overexpressed, making it a potential target for drug discovery. The protease activity of separase is strictly regulated by the inhibitor securin, which forms a tight complex with separase and may also stabilize this enzyme. Separases are large, 140-250-kilodalton enzymes, with an amino-terminal alpha-helical region and a carboxy-terminal caspase-like catalytic domain. Although crystal structures of the C-terminal two domains of separase and low-resolution electron microscopy reconstructions of the separase-securin complex have been reported, the atomic structures of full-length separase and especially the complex with securin are unknown. Here we report crystal structures at up to 2.6 A resolution of the yeast Saccharomyces cerevisiae separase-securin complex. The alpha-helical region of separase (also known as Esp1) contains four domains (I-IV), and a substrate-binding domain immediately precedes the catalytic domain and has tight associations with it. The separase-securin complex assumes a highly elongated structure. Residues 258-373 of securin (Pds1), named the separase interaction segment, are primarily in an extended conformation and traverse the entire length of separase, interacting with all of its domains. Most importantly, residues 258-269 of securin are located in the separase active site, illuminating the mechanism of inhibition. Biochemical studies confirm the structural observations and indicate that contacts outside the separase active site are crucial for stabilizing the complex, thereby defining an important function for the helical region of separase. Molecular mechanism for the regulation of yeast separase by securin.,Luo S, Tong L Nature. 2017 Feb 9;542(7640):255-259. doi: 10.1038/nature21061. Epub 2017 Feb 1. PMID:28146474[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Separase | Luo, S | Tong, L | Chaperon | Chromosome segregation | Cohesion | Esp1 | Helical region | Hydrolase | Inhibition | Pds1 | Separase-securin complex
