Cryo-EM structures of the human volume-regulated anion channel LRRC8

Go Kasuya, Takanori Nakane, Takeshi Yokoyama, Yanyan Jia, Masato Inoue, Kengo Watanabe, Ryoki Nakamura, Tomohiro Nishizawa, Tsukasa Kusakizako, Akihisa Tsutsumi, Haruaki Yanagisawa, Naoshi Dohmae, Motoyuki Hattori, Hidenori Ichijo, Zhiqiang Yan, Masahide Kikkawa, Mikako Shirouzu, Ryuichiro Ishitani, Osamu Nureki

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by single-particle cryo-electron microscopy. The structure shows a hexameric assembly, and the transmembrane region features a topology similar to gap junction channels. The LRR region, with 15 leucine-rich repeats, forms a long, twisted arc. The channel pore is located along the central axis and constricted on the extracellular side, where highly conserved polar and charged residues at the tip of the extracellular helix contribute to permeability to anions and other osmolytes. Two structural populations were identified, corresponding to compact and relaxed conformations. Comparing the two conformations suggests that the LRR region is flexible and mobile, with rigid-body motions, which might be implicated in structural transitions on pore opening.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalNature Structural and Molecular Biology
Issue number9
Publication statusPublished - 2018 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Cryo-EM structures of the human volume-regulated anion channel LRRC8'. Together they form a unique fingerprint.

Cite this