Dataset Information

Structure of a volume-regulated heteromeric LRRC8A/C channel

ABSTRACT: Volume-regulated anion channels participate in the cellular response to osmotic swelling. These membrane proteins are heteromers of LRRC8 family members whose composition determines permeation properties. Although structures of the obligatory LRRC8A subunit have previously defined the architecture of VRACs, the organization of heteromeric channels has remained elusive. Here we have closed this gap by the structural characterization of channels consisting of LRRC8A and C. Like homomeric LRRC8A, these proteins assemble as hexamers. Despite the twelve possible arrangements, we find a single predominant species with an A/C ratio of two. In this assembly, the four LRRCA 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Antje Dittmann

LAB HEAD: Raimund Dutzler

PROVIDER: PXD035350 | Pride | 2023-01-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20211028_011_S323018_SIL_undil.raw	Raw
	20220524_002_S388485_endog_AC-cells_endogenous_AC_rep2.raw	Raw
	20220524_004_S388486_AC_1-1_5-final_1_1_transfection_rep.raw	Raw
	20220531_002_S389586_endog_AC_01_endogenous_AC.raw	Raw
	20220531_004_S389587_endog_AC_02_endogenous_AC.raw	Raw

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Publications

Structure of a volume-regulated heteromeric LRRC8A/C channel.

Rutz Sonja S Deneka Dawid D Dittmann Antje A Sawicka Marta M Dutzler Raimund R

Nature structural & molecular biology 20221215 1

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 LRR ...[more]

PMID: 36522427

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