PDBsum entry 4d7t

Transport protein

PDB id: 4d7t

Contents

Protein chains

197 a.a.

173 a.a.

Ligands

CMP ×2

Waters ×1

PDB id:

4d7t

Name:

Transport protein

Title:

Structure of the sthk carboxy-terminal region in complex with camp

Structure:

Sthk_cnbd_camp. Chain: a, b. Fragment: cyclic nucleotide binding domain, residues 226-423

Source:

Spirochaeta thermophila dsm 6192. Organism_taxid: 665571

Resolution:

2.58Å R-factor: 0.268 R-free: 0.310

Authors:

D.Kesters,M.Brams,M.Nys,E.Wijckmans,R.Spurny,T.Voets,J.Tytgat,C.Ulens

Key ref:

D.Kesters et al. (2015). Structure of the SthK carboxy-terminal region reveals a gating mechanism for cyclic nucleotide-modulated ion channels. PLoS One, 10, e0116369. PubMed id: 25625648

Date:

27-Nov-14 Release date: 11-Feb-15

Protein chain

E0RR11  (E0RR11_SPITD) -  Cyclic nucleotide-binding domain-containing protein from Spirochaeta thermophila (strain ATCC 49972 / DSM 6192 / RI 19.B1)

Seq: 430 a.a.

Struc: 197 a.a.

Protein chain

E0RR11  (E0RR11_SPITD) -  Cyclic nucleotide-binding domain-containing protein from Spirochaeta thermophila (strain ATCC 49972 / DSM 6192 / RI 19.B1)

Seq: 430 a.a.

Struc: 173 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

PLoS One 10:e0116369 (2015)

PubMed id: 25625648

Structure of the SthK carboxy-terminal region reveals a gating mechanism for cyclic nucleotide-modulated ion channels.

D.Kesters, M.Brams, M.Nys, E.Wijckmans, R.Spurny, T.Voets, J.Tytgat, J.Kusch, C.Ulens.

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.