3JXI

Crystal structure of the chicken TRPV4 ankyrin repeat domain

3JXI の概要

• エントリーDOI: 10.2210/pdb3jxi/pdb
• 関連するPDBエントリー: 2etb 2pnn 2rfa 3JZJ
• 分子名称: Vanilloid receptor-related osmotically activated channel protein (2 entities in total)
• 機能のキーワード: ankyrin repeats, ank repeat, ion transport, ionic channel, receptor, transmembrane, transport, membrane protein
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117915.56

構造登録者

Phelps, C.B.,Wang, R.R.,Gaudet, R. (登録日: 2009-09-19, 公開日: 2009-12-22, 最終更新日: 2023-09-06)

主引用文献

Landoure, G.,Zdebik, A.A.,Martinez, T.L.,Burnett, B.G.,Stanescu, H.C.,Inada, H.,Shi, Y.,Taye, A.A.,Kong, L.,Munns, C.H.,Choo, S.S.,Phelps, C.B.,Paudel, R.,Houlden, H.,Ludlow, C.L.,Caterina, M.J.,Gaudet, R.,Kleta, R.,Fischbeck, K.H.,Sumner, C.J.
Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
Nat.Genet., 42:170-174, 2010

PubMed Abstract: Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant linkage to chromosome 12q24.11. We sequenced all genes in this region and identified two heterozygous missense mutations in the TRPV4 gene, C805T and G806A, resulting in the amino acid substitutions R269C and R269H. TRPV4 is a well-known member of the TRP superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations caused marked cellular toxicity and increased constitutive and activated channel currents. Mutations in TRPV4 were previously associated with skeletal dysplasias. Our findings indicate that TRPV4 mutations can also cause a degenerative disorder of the peripheral nerves. The CMT2C-associated mutations lie in a distinct region of the TRPV4 ankyrin repeats, suggesting that this phenotypic variability may be due to differential effects on regulatory protein-protein interactions.

PubMed: 20037586
DOI: 10.1038/ng.512

実験手法

X-RAY DIFFRACTION (2.3 Å)