Molecular Mechanism of Lipid Recognition and Membrane-Guided Gating in Plant Minimal START Proteins
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
-
The hydrophobic nature of lipids requires specialized transport mechanisms, and one such non-vesicular transport mechanism involves StAR-related lipid transfer (START) domain proteins. Unlike multidomain variants, plant minimal START proteins remain poorly understood.
-
Integrating structural screening across representative plant species, including Arabidopsis thaliana, Solanum lycopersicum, Cicer arietinum, Glycine max and Oryza sativa , with experimental validation, we show these proteins specifically bind amphipathic lipids, primarily myristic acid and lysophosphatidylcholine. Detailed analysis via circular dichroism, molecular dynamics simulations, and subcellular localization focused on the Arabidopsis protein AT4G14500.
-
Ligand binding occurs through a bipartite mechanism where conserved basic cavity residues coordinate polar headgroups while hydrophobic tails sit deeper within the pocket. Mechanistically, ligand association induces closure of a lid-like β 5 -β 6 loop at the cavity entrance, whereas membrane proximity promotes gate reopening and lipid release, supporting a membrane-guided gating mechanism. Consistent with this model, confocal microscopy revealed AT4G14500 associates with key lipid metabolic sites: the endoplasmic reticulum, plastids, Golgi apparatus, and plasma membrane.
-
Together, our findings establish plant minimal START proteins as bona fide lipid-binding proteins that utilize a bipartite ligand-binding mechanism coupled with membrane-responsive gating dynamics.
Abstract Figure
Graphical Abstract.
Proposed model for ligand binding and membrane-associated gating in plant minimal START proteins . (1) In the apo state, the lid (β 5 –β 6 loop) adopts an open conformation that permits ligand entry into the hydrophobic cavity. (2) Ligand binding induces closure of the lid, resulting in entrapment of the lipid within the START-domain cavity. (3) Membrane proximity promotes reopening of the loop and facilitates lipid release toward the membrane.
