An intermolecular hydrogen bonded network in the PRELID-TRIAP protein family plays a role in lipid sensing

DOI: 10.1016/j.bbapap.2022.140867

Authors: Xeni Miliara (Imperial College London) , Takashi Tatsuta (Max Planck Institute for Biology of Ageing) , Akinori Eiyama (Max Planck Institute for Biology of Ageing) , Thomas Langer (Max Planck Institute for Biology of Ageing; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)) , Sarah L. Rouse (Imperial College London) , Steve Matthews (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochimica Et Biophysica Acta (bba) - Proteins And Proteomics , VOL 1871

State: Published (Approved)
Published: November 2022
Diamond Proposal Number(s): 9424

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.

Journal Keywords: Mitochondrial lipid transfer; PRELID-TRIAP1 family of proteins; PRELID3B; X-ray crystallography; Molecular dynamics simulation

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Added On: 24/11/2022 08:49

Documents:
1-s2.0-S1570963922001145-main.pdf

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)