8k0b

Cryo-EM structure of TMEM63CCryo-EM structure of TMEM63C

Structural highlights

8k0b is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.56Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSC1_MOUSE Acts as an osmosensitive cation channel preferentially activated upon hypotonic stress (PubMed:27045885, PubMed:32375046, PubMed:37945568). Enriched in mitochondria-ER contact sites where it may regulate the metabolite flux and organelles' morphologies in response to osmotic changes. In particular may regulate mitochondrial motility and function in motor neuron axons (By similarity). Required for the functional integrity of the kidney glomerular filtration barrier (By similarity).[UniProtKB:D3ZNF5][UniProtKB:Q9P1W3]^[1] ^[2] ^[3]

Publication Abstract from PubMed

The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 A, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Cryo-EM structure of TMEM63C suggests it functions as a monomer.,Qin Y, Yu D, Wu D, Dong J, Li WT, Ye C, Cheung KC, Zhang Y, Xu Y, Wang Y, Shi YS, Dang S Nat Commun. 2023 Nov 9;14(1):7265. doi: 10.1038/s41467-023-42956-2. PMID:37945568^[4]

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

References

↑ Zhao X, Yan X, Liu Y, Zhang P, Ni X. Co-expression of mouse TMEM63A, TMEM63B and TMEM63C confers hyperosmolarity activated ion currents in HEK293 cells. Cell Biochem Funct. 2016 Jun;34(4):238-41. PMID:27045885 doi:10.1002/cbf.3185
↑ Du H, Ye C, Wu D, Zang YY, Zhang L, Chen C, He XY, Yang JJ, Hu P, Xu Z, Wan G, Shi YS. The Cation Channel TMEM63B Is an Osmosensor Required for Hearing. Cell Rep. 2020 May 5;31(5):107596. PMID:32375046 doi:10.1016/j.celrep.2020.107596
↑ Qin Y, Yu D, Wu D, Dong J, Li WT, Ye C, Cheung KC, Zhang Y, Xu Y, Wang Y, Shi YS, Dang S. Cryo-EM structure of TMEM63C suggests it functions as a monomer. Nat Commun. 2023 Nov 9;14(1):7265. PMID:37945568 doi:10.1038/s41467-023-42956-2
↑ Qin Y, Yu D, Wu D, Dong J, Li WT, Ye C, Cheung KC, Zhang Y, Xu Y, Wang Y, Shi YS, Dang S. Cryo-EM structure of TMEM63C suggests it functions as a monomer. Nat Commun. 2023 Nov 9;14(1):7265. PMID:37945568 doi:10.1038/s41467-023-42956-2

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OCA

[1] Zhao X, Yan X, Liu Y, Zhang P, Ni X. Co-expression of mouse TMEM63A, TMEM63B and TMEM63C confers hyperosmolarity activated ion currents in HEK293 cells. Cell Biochem Funct. 2016 Jun;34(4):238-41. PMID:27045885 doi:10.1002/cbf.3185

[2] Du H, Ye C, Wu D, Zang YY, Zhang L, Chen C, He XY, Yang JJ, Hu P, Xu Z, Wan G, Shi YS. The Cation Channel TMEM63B Is an Osmosensor Required for Hearing. Cell Rep. 2020 May 5;31(5):107596. PMID:32375046 doi:10.1016/j.celrep.2020.107596

[3] Qin Y, Yu D, Wu D, Dong J, Li WT, Ye C, Cheung KC, Zhang Y, Xu Y, Wang Y, Shi YS, Dang S. Cryo-EM structure of TMEM63C suggests it functions as a monomer. Nat Commun. 2023 Nov 9;14(1):7265. PMID:37945568 doi:10.1038/s41467-023-42956-2

[4] Qin Y, Yu D, Wu D, Dong J, Li WT, Ye C, Cheung KC, Zhang Y, Xu Y, Wang Y, Shi YS, Dang S. Cryo-EM structure of TMEM63C suggests it functions as a monomer. Nat Commun. 2023 Nov 9;14(1):7265. PMID:37945568 doi:10.1038/s41467-023-42956-2

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