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Structural basis of intramitochondrial phosphatidic acid transport mediated by U ps1‐ M dm35 complex
Author(s) -
Yu Fang,
He Fangyuan,
Yao Hongyan,
Wang Chengyuan,
Wang Jianchuan,
Li Jianxu,
Qi Xiaofeng,
Xue Hongwei,
Ding Jianping,
Zhang Peng
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540137
Subject(s) - phosphatidic acid , antiparallel (mathematics) , chemistry , biophysics , cardiolipins , helix (gastropod) , phospholipid , biochemistry , membrane , stereochemistry , cardiolipin , biology , ecology , physics , quantum mechanics , snail , magnetic field
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 MSF 1/ PRELI family proteins.