6I4Y

X-ray structure of the human mitochondrial PRELID3b-TRIAP1 complex

Summary for 6I4Y

• Entry DOI: 10.2210/pdb6i4y/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose transport system, substrate-binding protein,TP53-regulated inhibitor of apoptosis 1, PRELI domain containing protein 3B, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: mitochondrial lipid transport, complex, phospholipid transporter, apoptosis, phosphatidylserine, ps transport, lipid transport
• Biological source: Escherichia coli; More
• Total number of polymer chains: 2
• Total formula weight: 72431.93

Authors

Miliara, X.,Berry, J.-L.,Morgan, R.M.L.,Matthews, S.J. (deposition date: 2018-11-12, release date: 2019-03-20, Last modification date: 2024-11-06)

Primary citation

Miliara, X.,Tatsuta, T.,Berry, J.L.,Rouse, S.L.,Solak, K.,Chorev, D.S.,Wu, D.,Robinson, C.V.,Matthews, S.,Langer, T.
Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins.
Nat Commun, 10:1130-1130, 2019

PubMed 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.

PubMed: 30850607
DOI: 10.1038/s41467-019-09089-x

Experimental method

X-RAY DIFFRACTION (2.91 Å)