RT Journal Article
SR Electronic
T1 Structure and dynamics of human perilipin 3 membrane association
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.17.516819
DO 10.1101/2022.11.17.516819
A1 Yong Mi Choi
A1 Dalila Ajjaji
A1 Kaelin D. Fleming
A1 Peter P. Borbat
A1 Meredith L. Jenkins
A1 Brandon E Moeller
A1 Jack H. Freed
A1 John E. Burke
A1 Abdou Rachid Thiam
A1 Michael V. Airola
YR 2022
UL http://biorxiv.org/content/early/2022/11/17/2022.11.17.516819.abstract
AB Lipid droplets (LDs) are dynamic organelles that contain an oil core mainly composed of triglycerides (TAG) that is surrounded by a phospholipid monolayer and LD-associated proteins called perilipins (PLINs). During LD biogenesis, perilipin 3 (PLIN3) is recruited to nascent LDs as they emerge from the endoplasmic reticulum. Here, we analyzed how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding. We found the TAG precursors phosphatidic acid and diacylglycerol (DAG) recruit PLIN3 to membrane bilayers and define an expanded PAT domain that preferentially binds DAG enriched membranes. Membrane binding induces a disorder/order transition of alpha helices within the PAT domain and 11-mer repeats, with intramolecular distance measurements consistent with the expanded PAT domain adopting a triangular tertiary structure. In cells, PLIN3 is recruited to DAG enriched ER membranes, and this requires both the PAT domain and 11-mer repeats. This provides molecular details of PLIN3 recruitment to nascent LDs and identifies a function of the PAT domain of PLIN3 in DAG binding.Competing Interest StatementJEB reports personal fees from Scorpion Therapeutics and Olema Oncology; and research grants from Novartis.