Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
| Autor: | Christopher G. Burd, Yiying Cai, Yongqiang Deng, Florian A. Horenkamp, Karin M. Reinisch |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Saccharomyces cerevisiae Proteins Green Fluorescent Proteins Golgi Apparatus Saccharomyces cerevisiae Biology Crystallography X-Ray Endoplasmic Reticulum Catalysis Phosphoinositide Phosphatases symbols.namesake chemistry.chemical_compound Phosphatidylinositol Phosphates Report Phosphatidylinositol Research Articles Secretory pathway Endoplasmic reticulum Membrane Proteins Cell Biology Golgi apparatus Phosphoric Monoester Hydrolases Protein Structure Tertiary 3. Good health Cell biology Organelle membrane Pleckstrin homology domain chemistry Multiprotein Complexes symbols Medial Golgi Carrier Proteins Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201404041 |
| Popis: | Characterization of the structure of the N-terminal portion of yeast Sac1 in complex with the phosphatidylinositol 4-kinase effector Vps74 identifies how Sac1 is directed to dephosphorylate PtdIns4P in the Golgi. Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, containing the conserved Sac1 homology domain, in complex with Vps74, a phosphatidylinositol 4-kinase effector and the orthologue of human GOLPH3. The interface involves the N-terminal subdomain of the Sac1 homology domain, within which mutations in the related Sac3/Fig4 phosphatase have been linked to Charcot–Marie–Tooth disorder CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1–Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase. The analysis prompts a revision of the membrane-docking mechanism for GOLPH3 family proteins and reveals how an effector of phosphoinositide signaling serves a dual function in signal termination. |
| Databáze: | OpenAIRE |
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