taste / assembly / calcium homeostasis modulator protein / membrane protein / channel / lipid binding / large-pore channel
機能・相同性
機能・相同性情報
Sensory perception of salty taste / ATP transport / sensory perception of bitter taste / sensory perception of umami taste / ATP export / sensory perception of sweet taste / protein heterooligomerization / voltage-gated monoatomic ion channel activity / calcium-activated cation channel activity / regulation of monoatomic ion transmembrane transport ...Sensory perception of salty taste / ATP transport / sensory perception of bitter taste / sensory perception of umami taste / ATP export / sensory perception of sweet taste / protein heterooligomerization / voltage-gated monoatomic ion channel activity / calcium-activated cation channel activity / regulation of monoatomic ion transmembrane transport / monoatomic cation transport / voltage-gated calcium channel activity / monoatomic cation channel activity / protein homooligomerization / Sensory perception of sweet, bitter, and umami (glutamate) taste / basolateral plasma membrane / endoplasmic reticulum membrane / identical protein binding / plasma membrane 類似検索 - 分子機能
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
米国
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red. 著者: Johanna L Syrjänen / Max Epstein / Ricardo Gómez / Hiro Furukawa / 要旨: Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into ...Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into functional regulation, pore architecture, and channel blockade remain limited. Here we present the cryo-EM structure of human CALHM1, revealing an octameric assembly pattern similar to the non-mammalian CALHM1s and the lipid-binding pocket conserved across species. We demonstrate by MD simulations that this pocket preferentially binds a phospholipid over cholesterol to stabilize its structure and regulate the channel activities. Finally, we show that residues in the amino-terminal helix form the channel pore that ruthenium red binds and blocks.