4TU3

Crystal structure of yeast Sac1/Vps74 complex

Summary for 4TU3

• Entry DOI: 10.2210/pdb4tu3/pdb
• Descriptor: Phosphoinositide phosphatase SAC1, Vacuolar protein sorting-associated protein 74 (2 entities in total)
• Functional Keywords: protein complex, phosphoric monoester hydrolases, phosphatidylinositol phosphates, golgi apparatus, hydrolase-protein transport complex, hydrolase/protein transport
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Endoplasmic reticulum membrane; Single-pass membrane protein: P32368; Golgi apparatus, Golgi stack membrane; Peripheral membrane protein; Cytoplasmic side: Q06385
• Total number of polymer chains: 2
• Total formula weight: 110549.09

Authors

Cai, Y.,Horenkamp, F.A.,Reinisch, K.R. (deposition date: 2014-06-23, release date: 2014-08-27, Last modification date: 2023-09-27)

Primary citation

Cai, Y.,Deng, Y.,Horenkamp, F.,Reinisch, K.M.,Burd, C.G.
Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus.
J.Cell Biol., 206:485-491, 2014

PubMed Abstract: 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.

PubMed: 25113029
DOI: 10.1083/jcb.201404041

Experimental method

X-RAY DIFFRACTION (3.187 Å)