9YQP

Cryo-EM structure of the VPS13C N-terminal region in complex with Calmodulin

This is a non-PDB format compatible entry.

Summary for 9YQP

• Entry DOI: 10.2210/pdb9yqp/pdb
• EMDB information: 73343
• Descriptor: Calmodulin-1, Intermembrane lipid transfer protein VPS13C (2 entities in total)
• Functional Keywords: lipid transport protein; bltp; membrane repair; membrane homeostasis; vps13c, 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: 2025-10-15, release date: 2026-06-10, Last modification date: 2026-07-29)

Primary citation

Li, D.,Wang, X.,Hao, H.,Eden, J.,Hu, B.,Walsh, E.E.,Parson, M.A.H.,Hamill, S.,Li, Y.,Chen, G.,Burke, J.E.,De Camilli, P.,Reinisch, K.M.
Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.
Mol.Cell, 86:2843-, 2026

PubMed Abstract: Bridge-like lipid transfer proteins (BLTPs) play fundamental roles in cellular lipid redistribution between organellar membranes. They comprise bridge domains spanning organelles at contact sites that allow lipids to transit through the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables lipid transfer. To address the mechanisms underlying the assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinson's disease protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, in which the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin (CaM), central to calcium signaling, as a constitutive VPS13C interactor. Calcium induces conformational changes in the VPS13C-CaM complex, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as a starting point for understanding its regulation and that of other VPS13 proteins.

PubMed: 42413490
DOI: 10.1016/j.molcel.2026.06.028

Experimental method

ELECTRON MICROSCOPY (4.1 Å)