9JJE

Nematostella vectensis TRPM2 tetramer in complex with ADPRP/Ca2+

9JJE の概要

• エントリーDOI: 10.2210/pdb9jje/pdb
• EMDBエントリー: 61524
• 分子名称: Transient receptor potential cation channel subfamily M member-like 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: nematostella vectensis, trpm2, adprp, ca2+, membrane protein
• 由来する生物種: Nematostella vectensis (starlet sea anemone)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 711068.85

構造登録者

Jiang, Y.,Zhang, Z.,Toth, B.,Szollosi, A.,Csanady, L. (登録日: 2024-09-13, 公開日: 2024-11-06, 最終更新日: 2024-12-18)

主引用文献

Toth, B.,Jiang, Y.,Szollosi, A.,Zhang, Z.,Csanady, L.
A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel.
Proc.Natl.Acad.Sci.USA, 121:e2415548121-e2415548121, 2024

PubMed Abstract: Transient Receptor Potential Melastatin 2 (TRPM2) cation channels contribute to immunocyte activation, insulin secretion, and central thermoregulation. TRPM2 opens upon binding cytosolic Ca and ADP ribose (ADPR). We present here the 2.5 Å cryo-electronmicroscopy structure of TRPM2 from (nvTRPM2) in a lipid nanodisc, complexed with Ca and ADPR-2'-phosphate. Comparison with nvTRPM2 without nucleotide reveals that nucleotide binding-induced movements in the protein's three "core" layers deconvolve into a set of rigid-body rotations conserved from cnidarians to man. By covalently crosslinking engineered cysteine pairs we systematically trap the cytosolic layers in specific conformations and study effects on gate opening/closure. The data show that nucleotide binding in Layer 3 disrupts inhibitory intersubunit interactions, allowing rotation of Layer 2 which in turn expands the gate located in Layer 1. Channels trapped in that "activated" state are no longer nucleotide dependent, but are opened by binding of Ca alone.

PubMed: 39514307
DOI: 10.1073/pnas.2415548121

実験手法

ELECTRON MICROSCOPY (2.52 Å)