9YRP

Full-length human VPS13C in complex with calmodulin from the CryoEM composite map

This is a non-PDB format compatible entry.

Summary for 9YRP

• Entry DOI: 10.2210/pdb9yrp/pdb
• EMDB information: 73373
• Descriptor: Calmodulin-1, Intermembrane lipid transfer protein VPS13C (2 entities in total)
• Functional Keywords: lipid transport protein; bltp; lysosomal membrane repair; membrane homeostasis, lipid transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 442727.98

Authors

Li, D.,Reinisch, K.M. (deposition date: 2025-10-16, release date: 2026-06-10)

Primary citation

Li, D.,Wang, X.,Hu, B.,Hao, H.,Hamill, S.,Li, Y.,Chen, G.,De Camilli, P.,Reinisch, K.M.
Insights into the regulation of VPS13 family bridge-like lipid transfer proteins from the structure of VPS13C.
Biorxiv,

PubMed Abstract: Bridge-like lipid transfer proteins (BLTPs) play central roles in redistributing lipids from their primary site of synthesis in the endoplasmic reticulum to other organelles. They comprise bridge-domains spanning between organelles at contact sites that allow lipids to transit the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables their lipid transfer ability. To address the mechanisms underlying assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinson's protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, where the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin, central to calcium signaling, as a VPS13 partner, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as starting point to understand its regulation and, more broadly, that of other BLTPs.

PubMed: 41292763
DOI: 10.1101/2025.11.10.687702

Experimental method

ELECTRON MICROSCOPY (4.13 Å)