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-Structure paper
タイトル | Structure of a volume-regulated heteromeric LRRC8A/C channel. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 1, Page 52-61, Year 2023 |
掲載日 | 2022年12月15日 |
著者 | Sonja Rutz / Dawid Deneka / Antje Dittmann / Marta Sawicka / Raimund Dutzler / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:36522427 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.1 - 18.2 Å |
構造データ | EMDB-15835: Cryo-EM structure of homomeric LRRC8C Volume-Regulated Anion Channel EMDB-15836: Cryo-EM structure of heteromeric LRRC8A/C (1:1 co-transfected) Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1 EMDB-15837: Cryo-EM structure of heteromeric LRRC8A/C Volume-Regulated Anion Channel EMDB-15838: Cryo-EM structure of heteromeric LRRC8A/C (1:3 co-transfected) Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1 EMDB-15839: Cryo-EM structure of heteromeric LRRC8A/C (endogenous) Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1 EMDB-15840: Cryo-EM structure of homomeric LRRC8A_SAM Volume-Regulated Anion Channel EMDB-15841: Cryo-EM structure of heteromeric LRRC8A_SAM/C Volume-Regulated Anion Channel PDB-8ben: |
由来 |
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キーワード | MEMBRANE PROTEIN / Ion channel / Volume-regulated anion channel |