4D7S

Structure of the SthK Carboxy-Terminal Region in complex with cGMP

4D7S の概要

• エントリーDOI: 10.2210/pdb4d7s/pdb
• 関連するPDBエントリー: 4D7T
• 分子名称: STHK_CNBD_CGMP, CYCLIC GUANOSINE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: transport protein
• 由来する生物種: SPIROCHAETA THERMOPHILA DSM 6192
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47087.80

構造登録者

Kesters, D.,Brams, M.,Nys, M.,Wijckmans, E.,Spurny, R.,Voets, T.,Tytgat, J.,Ulens, C. (登録日: 2014-11-27, 公開日: 2015-02-11, 最終更新日: 2023-12-20)

主引用文献

Kesters, D.,Brams, M.,Nys, M.,Wijckmans, E.,Spurny, R.,Voets, T.,Tytgat, J.,Kusch, J.,Ulens, C.
Structure of the SthK Carboxy-Terminal Region Reveals a Gating Mechanism for Cyclic Nucleotide-Modulated Ion Channels.
Plos One, 10:16369-, 2015

PubMed Abstract: Cyclic nucleotide-sensitive ion channels are molecular pores that open in response to cAMP or cGMP, which are universal second messengers. Binding of a cyclic nucleotide to the carboxyterminal cyclic nucleotide binding domain (CNBD) of these channels is thought to cause a conformational change that promotes channel opening. The C-linker domain, which connects the channel pore to this CNBD, plays an important role in coupling ligand binding to channel opening. Current structural insight into this mechanism mainly derives from X-ray crystal structures of the C-linker/CNBD from hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels. However, these structures reveal little to no conformational changes upon comparison of the ligand-bound and unbound form. In this study, we take advantage of a recently identified prokaryote ion channel, SthK, which has functional properties that strongly resemble cyclic nucleotide-gated (CNG) channels and is activated by cAMP, but not by cGMP. We determined X-ray crystal structures of the C-linker/CNBD of SthK in the presence of cAMP or cGMP. We observe that the structure in complex with cGMP, which is an antagonist, is similar to previously determined HCN channel structures. In contrast, the structure in complex with cAMP, which is an agonist, is in a more open conformation. We observe that the CNBD makes an outward swinging movement, which is accompanied by an opening of the C-linker. This conformation mirrors the open gate structures of the Kv1.2 channel or MthK channel, which suggests that the cAMP-bound C-linker/CNBD from SthK represents an activated conformation. These results provide a structural framework for better understanding cyclic nucleotide modulation of ion channels, including HCN and CNG channels.

PubMed: 25625648
DOI: 10.1371/JOURNAL.PONE.0116369

実験手法

X-RAY DIFFRACTION (2.55 Å)