5KHG

HCN2 CNBD in complex with cytidine-3', 5'-cyclic monophosphate (cCMP)

Summary for 5KHG

• Entry DOI: 10.2210/pdb5khg/pdb
• Related: 5KHH 5KHI 5KHJ 5KHK
• Descriptor: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, 4-amino-1-[(2S,4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]pyrimidin-2(1H)-one (3 entities in total)
• Functional Keywords: protein-ligand complex, cycilc nucleotide binding domain, ion transport, transport protein
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell membrane ; Multi-pass membrane protein : O88703
• Total number of polymer chains: 1
• Total formula weight: 24188.51

Authors

Ng, L.C.T.,Putrenko, I.,Baronas, V.,Van Petegem, F.,Accili, E.A. (deposition date: 2016-06-14, release date: 2016-09-14, Last modification date: 2023-09-27)

Primary citation

Ng, L.C.,Putrenko, I.,Baronas, V.,Van Petegem, F.,Accili, E.A.
Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening.
Structure, 24:1629-1642, 2016

PubMed Abstract: Cyclic AMP is thought to facilitate the opening of the HCN2 channel by binding to a C-terminal domain and promoting or inhibiting interactions between subunits. Here, we correlated the ability of cyclic nucleotides to promote interactions of isolated HCN2 C-terminal domains in solution with their ability to facilitate channel opening. Cyclic IMP, a cyclic purine nucleotide, and cCMP, a cyclic pyrimidine nucleotide, bind to a C-terminal domain containing the cyclic nucleotide-binding domain but, in contrast to other cyclic nucleotides examined, fail to promote its oligomerization, and produce only modest facilitation of opening of the full-length channel. Comparisons between ligand bound structures identify a region between the sixth and seventh β strands and the distal C helix as important for facilitation and tight binding. We propose that promotion of interactions between the C-terminal domains by a given ligand contribute to its ability to facilitate opening of the full-length channel.

PubMed: 27568927
DOI: 10.1016/j.str.2016.06.024

Experimental method

X-RAY DIFFRACTION (2.241 Å)