6FNW

Structure of a volume-regulated anion channel of the LRRC8 family

Summary for 6FNW

• Entry DOI: 10.2210/pdb6fnw/pdb
• Descriptor: Volume-regulated anion channel subunit LRRC8A, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: ion channel, leucine-rich repeat domain, membrane protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 48403.37

Authors

Deneka, D.,Sawicka, M.,Lam, A.K.M.,Paulino, C.,Dutzler, R. (deposition date: 2018-02-05, release date: 2018-05-16, Last modification date: 2024-05-08)

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

X-RAY DIFFRACTION (1.8 Å)