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.(2015) EMBO Rep 16: 813-823
- PubMed: 26071601 
- DOI: https://doi.org/10.15252/embr.201540137
- Primary Citation of Related Structures:  
4XHR, 4XIZ - PubMed 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 β-sheet and three α-helices. Mdm35 adopts a three-helical clamp-like structure to wrap around Ups1 to form a stable complex. The β-sheet and α-helices of Ups1 form a long tunnel-like pocket to accommodate the substrate PA, and a short helix α2 acts as a lid to cover the pocket. The hydrophobic residues lining the pocket and helix α2 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.
Organizational Affiliation: 
National Center for Protein Science Shanghai and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.