7y8w
Crystal structure of DLC-1/SAO-1 complex
Structural highlights
FunctionDYL1_CAEEL Acts as a non-catalytic accessory component of a dynein complex (By similarity). Part of a complex with bicd-1 and egal-1, which is recruited to the nuclear envelope by unc-83, where in turn, it recruits dynein to the nuclear surface and regulates nuclear migrations in hypodermal precursor cells (PubMed:20005871). Probably within a dynein motor complex, plays a role in the cell fate specification of the germline and oogenesis (PubMed:19752194, PubMed:27864381). In particular, it inhibits germ cell proliferation (PubMed:19752194). Regulates the function and localization of the RNA-binding protein fbf-2 in the germline (PubMed:27864381). Plays a role in mitotic and meiotic processes (PubMed:19752194, PubMed:26483555). Involved in the pairing of homologous chromosomes (PubMed:26483555). Independently of its dynein-mediated functions, plays a role in germ cell apoptosis (PubMed:24030151).[UniProtKB:Q24117][1] [2] [3] [4] [5] Publication Abstract from PubMedApoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two beta-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis. Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline.,Zhang D, Yang H, Jiang L, Zhao C, Wang M, Hu B, Yu C, Wei Z, Tse YC Cell Death Discov. 2022 Nov 3;8(1):441. doi: 10.1038/s41420-022-01233-9. PMID:36323675[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
