9YG5

VPS13A/Ct-XKR1

This is a non-PDB format compatible entry.

Summary for 9YG5

• Entry DOI: 10.2210/pdb9yg5/pdb
• EMDB information: 72913
• Descriptor: Endoplasmic reticulum membrane adapter protein XK, Intermembrane lipid transfer protein VPS13A (2 entities in total)
• Functional Keywords: vps13a, xkr1, bltps, scrambles, lipid transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 235071.07

Authors

Hu, B.,Reinisch, K.M. (deposition date: 2025-09-27, release date: 2026-06-10, Last modification date: 2026-07-01)

Primary citation

Hu, B.,Alvarez, D.,Rocha-Roa, C.,Guyard, V.,Li, D.,Ahmed, Y.,Wang, X.,De Camilli, P.,Vanni, S.,Reinisch, K.M.
Mechanism of lipid transfer by bridge-like protein VPS13A and the scramblase XK.
Cell, 2026

PubMed Abstract: In eukaryotes, bridge-like lipid-transfer proteins (BLTPs) are central in mediating vesicle-independent lipid transfer between organelles. BLTPs span the cytosolic space between organelles at contact sites, featuring hydrophobic channels for lipids to travel between membranes. How BLTPs cooperate with partner proteins to orchestrate lipid delivery remains a mystery. Here, we used cryo-electron microscopy to visualize a complex comprising the prototypical BLTP VPS13A and the plasma membrane-localized scramblase XK at near-atomic resolution. VPS13A interacts with XK via its pleckstrin homology domain, priming VPS13A's bridge-like lipid-transfer domain to deliver lipids directly to the cytosolic leaflet of the acceptor membrane. In molecular dynamics simulations, this arrangement allows for robust lipid transfer. Newly delivered lipids can then be equilibrated between leaflets of the membrane bilayer by the scramblase, allowing for membrane growth. Mechanistic insights regarding lipid delivery by VPS13A are directly applicable to all VPS13 proteins and, more broadly, to all BLTP family members.

PubMed: 42285089
DOI: 10.1016/j.cell.2026.05.027

Experimental method

ELECTRON MICROSCOPY (3.41 Å)