Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex.

ABSTRACT: Ups1 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 ?-sheet and three ?-helices. Mdm35 adopts a three-helical clamp-like structure to wrap around Ups1 to form a stable complex. The ?-sheet and ?-helices of Ups1 form a long tunnel-like pocket to accommodate the substrate PA, and a short helix ?2 acts as a lid to cover the pocket. The hydrophobic residues lining the pocket and helix ?2 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.

SUBMITTER: Yu F 

PROVIDER: S-EPMC4515121 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature