8b40
From Proteopedia
Structure of homomeric LRRC8C Volume-Regulated Anion Channel
Structural highlights
FunctionLRC8C_MOUSE Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (By similarity). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (By similarity). May play a role in adipogenesis (PubMed:15184384, PubMed:15564382, PubMed:21804215).[UniProtKB:Q8TDW0][1] [2] [3] [4] Publication Abstract from PubMedVolume-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. Structure of a volume-regulated heteromeric LRRC8A/C channel.,Rutz S, Deneka D, Dittmann A, Sawicka M, Dutzler R Nat Struct Mol Biol. 2023 Jan;30(1):52-61. doi: 10.1038/s41594-022-00899-0. Epub , 2022 Dec 15. PMID:36522427[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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