4xhr | pdb_00004xhr
Structure of a phospholipid trafficking complex, native
Structural highlights
Function[UPS1_YEAST] Required for maintenance of normal mitochondrial morphology as well as PCP1-dependent processing of MGM1. With UPS2, controls the level of cardiolipin in mitochondria. Cardiolipin is a unique phospholipid with four fatty acid chains and is present mainly in the mitochondrial inner membrane where it stabilizes the electron transport chain supercomplex between complexes III and IV through direct interaction of their subunits.[1] [2] [3] [4] [MDM35_YEAST] Involved in mitochondrial distribution and morphology. Mediates the import of UPS1, UPS2 and UPS3, 3 atypical mitochondrial intermembrane space (IMS) proteins lacking the two major IMS-targeting signals, into the intermembrane space.[5] [6] [7] Publication Abstract from PubMedUps1 forms a complex with Mdm35 and is critical for the transport of phosphatidic acid (PA) from the mitochondrial outer membrane to the inner membrane. We report the crystal structure of the Ups1-Mdm35-PA complex and the functional characterization of Ups1-Mdm35 in PA binding and transfer. Ups1 features a barrel-like structure consisting of an antiparallel beta-sheet and three alpha-helices. Mdm35 adopts a three-helical clamp-like structure to wrap around Ups1 to form a stable complex. The beta-sheet and alpha-helices of Ups1 form a long tunnel-like pocket to accommodate the substrate PA, and a short helix alpha2 acts as a lid to cover the pocket. The hydrophobic residues lining the pocket and helix alpha2 are critical for PA binding and transfer. In addition, a hydrophilic patch on the surface of Ups1 near the PA phosphate-binding site also plays an important role in the function of Ups1-Mdm35. Our study reveals the molecular basis of the function of Ups1-Mdm35 and sheds new light on the mechanism of intramitochondrial phospholipid transport by the MSF1/PRELI family proteins. Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex.,Yu F, He F, Yao H, Wang C, Wang J, Li J, Qi X, Xue H, Ding J, Zhang P EMBO Rep. 2015 Jun 12. pii: e201540137. PMID:26071601[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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