Imperial College London
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DrSarahRouse

Faculty of Natural Sciences, Department of Life Sciences

UKRI Future Leaders Fellow
 
 
 
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Contact

 

s.rouse

 
 
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Location

 

Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Miliara:2019:10.1038/s41467-019-09089-x,
author = {Miliara, X and Tatsuta, T and Berry, J-L and Rouse, SL and Solak, K and Chorev, DS and Wu, D and Robinson, CV and Matthews, S and Langer, T},
doi = {10.1038/s41467-019-09089-x},
journal = {Nature Communications},
pages = {1--15},
title = {Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins},
url = {http://dx.doi.org/10.1038/s41467-019-09089-x},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Miliara,X
AU  - Tatsuta,T
AU  - Berry,J-L
AU  - Rouse,SL
AU  - Solak,K
AU  - Chorev,DS
AU  - Wu,D
AU  - Robinson,CV
AU  - Matthews,S
AU  - Langer,T
DO  - 10.1038/s41467-019-09089-x
EP  - 15
PY  - 2019///
SN  - 2041-1723
SP  - 1
TI  - Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-09089-x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000460631100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41467-019-09089-x
UR  - http://hdl.handle.net/10044/1/77386
VL  - 10
ER  -
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