6BOA

Cryo-EM structure of human TRPV6-R470E in amphipols

6BOA の概要

• エントリーDOI: 10.2210/pdb6boa/pdb
• EMDBエントリー: 7120 7121 7122 7123
• 分子名称: Transient receptor potential cation channel subfamily V member 6 (1 entity in total)
• 機能のキーワード: ion channel, membrane protein, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 340563.50

構造登録者

McGoldrick, L.L.,Singh, A.K.,Saotome, K.,Yelshanskaya, M.V.,Twomey, E.C.,Grassucci, R.A.,Sobolevsky, A.I. (登録日: 2017-11-18, 公開日: 2017-12-20, 最終更新日: 2025-05-28)

主引用文献

McGoldrick, L.L.,Singh, A.K.,Saotome, K.,Yelshanskaya, M.V.,Twomey, E.C.,Grassucci, R.A.,Sobolevsky, A.I.
Opening of the human epithelial calcium channel TRPV6.
Nature, 553:233-237, 2018

PubMed Abstract: Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with a variety of human diseases, including cancers. TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside; it increases substantially in the presence of phosphatidylinositol 4,5-bisphosphate. Crystal structures of detergent-solubilized rat TRPV6 in the closed state have previously been solved. Corroborating electrophysiological results, these structures demonstrated that the Ca selectivity of TRPV6 arises from a ring of aspartate side chains in the selectivity filter that binds Ca tightly. However, how TRPV6 channels open and close their pores for ion permeation has remained unclear. Here we present cryo-electron microscopy structures of human TRPV6 in the open and closed states. The channel selectivity filter adopts similar conformations in both states, consistent with its explicit role in ion permeation. The iris-like channel opening is accompanied by an α-to-π-helical transition in the pore-lining transmembrane helix S6 at an alanine hinge just below the selectivity filter. As a result of this transition, the S6 helices bend and rotate, exposing different residues to the ion channel pore in the open and closed states. This gating mechanism, which defines the constitutive activity of TRPV6, is, to our knowledge, unique among tetrameric ion channels and provides structural insights for understanding their diverse roles in physiology and disease.

PubMed: 29258289
DOI: 10.1038/nature25182

実験手法

ELECTRON MICROSCOPY (4.2 Å)