Universität zu Köln

Miliara, Xeni, Tatsuta, Takashi, Berry, Jamie-Lee, Rouse, Sarah L., Solak, Kuebra, Chorev, Dror S., Wu, Di, Robinson, Carol V., Matthews, Stephen and Langer, Thomas (2019). Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

Conserved lipid transfer proteins of the Ups/PRELI family regulate lipid accumulation in mitochondria by shuttling phospholipids in a lipid-specific manner across the intermembrane space. Here, we combine structural analysis, unbiased genetic approaches in yeast and molecular dynamics simulations to unravel determinants of lipid specificity within the conserved Ups/PRELI family. We present structures of human PRELID1-TRIAP1 and PRELID3b-TRIAP1 complexes, which exert lipid transfer activity for phosphatidic acid and phosphatidylserine, respectively. Reverse yeast genetic screens identify critical amino acid exchanges that broaden and swap their lipid specificities. We find that amino acids involved in head group recognition and the hydrophobicity of flexible loops regulate lipid entry into the binding cavity. Molecular dynamics simulations reveal different membrane orientations of PRELID1 and PRELID3b during the stepwise release of lipids. Our experiments thus define the structural determinants of lipid specificity and the dynamics of lipid interactions by Ups/PRELI proteins.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Miliara, Xeni UNSPECIFIED UNSPECIFIED UNSPECIFIED Tatsuta, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Berry, Jamie-Lee UNSPECIFIED UNSPECIFIED UNSPECIFIED Rouse, Sarah L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Solak, Kuebra UNSPECIFIED UNSPECIFIED UNSPECIFIED Chorev, Dror S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wu, Di UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Carol V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthews, Stephen UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-154042
DOI:	10.1038/s41467-019-09089-x
Journal or Publication Title:	Nat. Commun.
Volume:	10
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAMITOCHONDRIAL TRANSPORT; PHOSPHOLIPID TRANSFER; INTERMEMBRANE SPACE; PHOSPHATIDIC-ACID; MITOCHONDRIAL; CARDIOLIPIN; YEAST; PHOSPHATIDYLETHANOLAMINE; ORGANIZATION; TRAFFICKING Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15404