6G9O

Structure of full-length homomeric mLRRC8A volume-regulated anion channel at 4.25 A resolution

Summary for 6G9O

• Entry DOI: 10.2210/pdb6g9o/pdb
• Related: 6G8Z 6G9L
• EMDB information: 4361 4362 4366 4367
• Descriptor: Volume-regulated anion channel subunit LRRC8A (1 entity in total)
• Functional Keywords: chloride channel, swelling-activated, vsoac, leucine-rich repeat, membrane protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 6
• Total formula weight: 565436.30

Authors

Sawicka, M.,Deneka, D.,Lam, A.K.M.,Paulino, C.,Dutzler, R. (deposition date: 2018-04-11, release date: 2018-05-16, Last modification date: 2024-10-23)

Primary citation

Deneka, D.,Sawicka, M.,Lam, A.K.M.,Paulino, C.,Dutzler, R.
Structure of a volume-regulated anion channel of the LRRC8 family.
Nature, 558:254-259, 2018

PubMed Abstract: Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.

PubMed: 29769723
DOI: 10.1038/s41586-018-0134-y

Experimental method

ELECTRON MICROSCOPY (4.25 Å)