8AG0

Crystal structure of mutant PRELID3a-TRIAP1 complex - R53E

Summary for 8AG0

• Entry DOI: 10.2210/pdb8ag0/pdb
• Descriptor: PRELI domain containing protein 3A, Maltose/maltodextrin-binding periplasmic protein,TP53-regulated inhibitor of apoptosis 1, alpha-D-glucopyranose-(1-4)-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, phospholipid transport, mitochondria, lipid transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 70243.52

Authors

Milara, X.,Perez-Dorado, J.I.,Matthews, S.J. (deposition date: 2022-07-18, release date: 2022-11-23, Last modification date: 2024-11-13)

Primary citation

Miliara, X.,Tatsuta, T.,Eiyama, A.,Langer, T.,Rouse, S.L.,Matthews, S.
An intermolecular hydrogen bonded network in the PRELID-TRIAP protein family plays a role in lipid sensing.
Biochim Biophys Acta Proteins Proteom, 1871:140867-140867, 2022

PubMed Abstract: The PRELID-TRIAP1 family of proteins is responsible for lipid transfer in mitochondria. Multiple structures have been resolved of apo and lipid substrate bound forms, allowing us to begin to piece together the molecular level details of the full lipid transfer cycle. Here, we used molecular dynamics simulations to demonstrate that the lipid binding is mediated by an extended, water-mediated hydrogen bonding network. A key mutation, R53E, was found to disrupt this network, causing lipid to be released from the complex. The X-ray crystal structure of R53E was captured in a fully closed and apo state. Lipid transfer assays and molecular simulations allow us to interpret the observed conformation in the context of the biological role. Together, our work provides further understanding of the mechanistic control of lipid transport by PRELID-TRIAP1 in mitochondria.

PubMed: 36309326
DOI: 10.1016/j.bbapap.2022.140867

Experimental method

X-RAY DIFFRACTION (2.7 Å)