6VSV

Crystal structure of a disease mutant of the Voltage-gated Sodium Channel Beta 4 subunit extracellular domain

6VSV の概要

• エントリーDOI: 10.2210/pdb6vsv/pdb
• 分子名称: Sodium channel subunit beta-4 (2 entities in total)
• 機能のキーワード: sodium channel, beta4 subunit, disease mutant, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14561.28

構造登録者

Das, S.,Van Petegem, F. (登録日: 2020-02-12, 公開日: 2020-08-26, 最終更新日: 2024-11-20)

主引用文献

Llongueras, J.P.,Das, S.,De Waele, J.,Capulzini, L.,Sorgente, A.,Van Petegem, F.,Bosmans, F.
Biophysical Investigation of Sodium Channel Interaction with beta-Subunit Variants Associated with Arrhythmias.
Bioelectricity, 2:269-278, 2020

PubMed Abstract: Voltage-gated sodium (Na) channels help regulate electrical activity of the plasma membrane. Mutations in associated subunits can result in pathological outcomes. Here we examined the interaction of Na channels with cardiac arrhythmia-linked mutations in and , two genes that encode auxiliary β-subunits. To investigate changes in and function, we combined three-dimensional X-ray crystallography with electrophysiological measurements on Na1.5, the dominant subtype in the heart. alters channel activity, whereas does not have an apparent effect. Structurally, the perturbation alters hydrophobic packing of the subunit with major structural changes and causes a thermal destabilization of the folding. In contrast, leads to structural changes but overall protein stability is unaffected. data suggest a functionally important region in the interaction between Na1.5 and β4 that, when disrupted, could lead to channel dysfunction. A lack of apparent functional effects of on Na1.5 suggests an alternative working mechanism, possibly through other Na channel subtypes present in heart tissue. Indeed, mapping the structural variations of onto neuronal Na channel structures suggests altered interaction patterns.

PubMed: 34476357
DOI: 10.1089/bioe.2020.0030

実験手法

X-RAY DIFFRACTION (1.62 Å)