8wua

cryo-EM structure of human TMEM63A

Structural highlights

8wua is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CSCL1_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

CSCL1_HUMAN Acts as an osmosensitive calcium-permeable cation channel (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938, PubMed:31587869, PubMed:37543036).[UniProtKB:Q91YT8]^[1] ^[2] ^[3]

Publication Abstract from PubMed

OSCA/TMEM63 is a newly identified family of mechanically activated (MA) ion channels in plants and animals, respectively, which convert physical forces into electrical signals or trigger intracellular cascades and are essential for eukaryotic physiology. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. However, the molecular architecture of the mammalian TMEM63 proteins remains unclear. Here we elucidate the structure of human TMEM63A in the presence of calcium by single particle cryo-EM, revealing a distinct monomeric architecture containing eleven transmembrane helices. It has structural similarity to the single subunit of the Arabidopsis thaliana OSCA proteins. We locate the ion permeation pathway within the monomeric configuration and observe a nonprotein density resembling lipid. These results lay a foundation for understanding the structural organization of OSCA/TMEM63A family proteins.

A monomeric structure of human TMEM63A protein.,Wu X, Shang T, Lu X, Luo D, Yang D Proteins. 2024 Jun;92(6):750-756. doi: 10.1002/prot.26660. Epub 2024 Jan 13. PMID:38217391^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, Ward AB, Patapoutian A. OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels. Elife. 2018 Nov 1;7:e41844. PMID:30382938 doi:10.7554/eLife.41844
↑ Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI. Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. Am J Hum Genet. 2019 Nov 7;105(5):996-1004. PMID:31587869 doi:10.1016/j.ajhg.2019.09.011
↑ Zheng W, Rawson S, Shen Z, Tamilselvan E, Smith HE, Halford J, Shen C, Murthy SE, Ulbrich MH, Sotomayor M, Fu TM, Holt JR. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron. 2023 Jul 28:S0896-6273(23)00512-3. PMID:37543036 doi:10.1016/j.neuron.2023.07.006
↑ Wu X, Shang T, Lü X, Luo D, Yang D. A monomeric structure of human TMEM63A protein. Proteins. 2024 Jun;92(6):750-756. PMID:38217391 doi:10.1002/prot.26660

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, Ward AB, Patapoutian A. OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels. Elife. 2018 Nov 1;7:e41844. PMID:30382938 doi:10.7554/eLife.41844

[2] Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI. Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. Am J Hum Genet. 2019 Nov 7;105(5):996-1004. PMID:31587869 doi:10.1016/j.ajhg.2019.09.011

[3] Zheng W, Rawson S, Shen Z, Tamilselvan E, Smith HE, Halford J, Shen C, Murthy SE, Ulbrich MH, Sotomayor M, Fu TM, Holt JR. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron. 2023 Jul 28:S0896-6273(23)00512-3. PMID:37543036 doi:10.1016/j.neuron.2023.07.006

[4] Wu X, Shang T, Lü X, Luo D, Yang D. A monomeric structure of human TMEM63A protein. Proteins. 2024 Jun;92(6):750-756. PMID:38217391 doi:10.1002/prot.26660

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8wua

cryo-EM structure of human TMEM63A

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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