7np4

cAMP-bound rabbit HCN4 stabilized in LMNG-CHS detergent mixture

spinqualitylabelsall models 7np4, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Ligands: CMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The HCN1-4 channel family is responsible for the hyperpolarization-activated cation current If/Ih that controls automaticity in cardiac and neuronal pacemaker cells. We present cryoelectron microscopy (cryo-EM) structures of HCN4 in the presence or absence of bound cAMP, displaying the pore domain in closed and open conformations. Analysis of cAMP-bound and -unbound structures sheds light on how ligand-induced transitions in the channel cytosolic portion mediate the effect of cAMP on channel gating and highlights the regulatory role of a Mg(2+) coordination site formed between the C-linker and the S4-S5 linker. Comparison of open/closed pore states shows that the cytosolic gate opens through concerted movements of the S5 and S6 transmembrane helices. Furthermore, in combination with molecular dynamics analyses, the open pore structures provide insights into the mechanisms of K(+)/Na(+) permeation. Our results contribute mechanistic understanding on HCN channel gating, cyclic nucleotide-dependent modulation, and ion permeation. Gating movements and ion permeation in HCN4 pacemaker channels.,Saponaro A, Bauer D, Giese MH, Swuec P, Porro A, Gasparri F, Sharifzadeh AS, Chaves-Sanjuan A, Alberio L, Parisi G, Cerutti G, Clarke OB, Hamacher K, Colecraft HM, Mancia F, Hendrickson WA, Siegelbaum SA, DiFrancesco D, Bolognesi M, Thiel G, Santoro B, Moroni A Mol Cell. 2021 Jun 18. pii: S1097-2765(21)00446-9. doi:, 10.1016/j.molcel.2021.05.033. PMID:34166608 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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