8B41

Structure of heteromeric LRRC8A/C (1:1 co-transfected) Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1

Summary for 8B41

• Entry DOI: 10.2210/pdb8b41/pdb
• Related: 8B41 8B42 8BEN
• EMDB information: 15835 15836 15837 15838 15839 15840 15841
• Descriptor: Volume-regulated anion channel subunit LRRC8A, Volume-regulated anion channel subunit LRRC8C, Synthetic nanobody Sb1 (3 entities in total)
• Functional Keywords: ion channel, volume-regulated anion channel, membrane protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 10
• Total formula weight: 619632.55

Authors

Sawicka, M.,Dutzler, R. (deposition date: 2022-09-19, release date: 2022-12-14, Last modification date: 2025-07-02)

Primary citation

Rutz, S.,Deneka, D.,Dittmann, A.,Sawicka, M.,Dutzler, R.
Structure of a volume-regulated heteromeric LRRC8A/C channel.
Nat.Struct.Mol.Biol., 30:52-61, 2023

PubMed Abstract: Volume-regulated anion channels (VRACs) participate in the cellular response to osmotic swelling. These membrane proteins consist of heteromeric assemblies of LRRC8 subunits, whose compositions determine permeation properties. Although structures of the obligatory LRRC8A, also referred to as SWELL1, have previously defined the architecture of VRACs, the organization of heteromeric channels has remained elusive. Here we have addressed this question by the structural characterization of murine LRRC8A/C channels. Like LRRC8A, these proteins assemble as hexamers. Despite 12 possible arrangements, we find a predominant organization with an A:C ratio of two. In this assembly, four LRRC8A subunits cluster in their preferred conformation observed in homomers, as pairs of closely interacting proteins that stabilize a closed state of the channel. In contrast, the two interacting LRRC8C subunits show a larger flexibility, underlining their role in the destabilization of the tightly packed A subunits, thereby enhancing the activation properties of the protein.

PubMed: 36522427
DOI: 10.1038/s41594-022-00899-0

Experimental method

ELECTRON MICROSCOPY (3.8 Å)