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PDBsum entry 3u11
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Transport protein
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PDB id
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3u11
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PDB id:
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| Name: |
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Transport protein
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Title:
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Tetramerization dynamics of thE C-terminus underlies isoform-specific camp-gating in hcn channels
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Structure:
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Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4. Chain: a, b. Fragment: c-terminal domain (unp residues 521-723). Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hcn4. Expressed in: escherichia coli. Expression_system_taxid: 562. Cassette
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Resolution:
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2.50Å
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R-factor:
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0.197
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R-free:
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0.277
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Authors:
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M.Lolicato,M.Nardini,S.Gazzarrini,S.Moller,D.Bertinetti,F.W.Herberg, M.Bolognesi,H.Martin,M.Fasolini,J.A.Bertrand,C.Arrigoni,G.Thiel, A.Moroni
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Key ref:
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M.Lolicato
et al.
(2011).
Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels.
J Biol Chem,
286,
44811-44820.
PubMed id:
DOI:
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Date:
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29-Sep-11
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Release date:
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26-Oct-11
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PROCHECK
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Headers
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References
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Q9Y3Q4
(HCN4_HUMAN) -
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 from Homo sapiens
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Seq:
Struc:
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1203 a.a.
198 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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J Biol Chem
286:44811-44820
(2011)
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PubMed id:
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Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels.
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M.Lolicato,
M.Nardini,
S.Gazzarrini,
S.Möller,
D.Bertinetti,
F.W.Herberg,
M.Bolognesi,
H.Martin,
M.Fasolini,
J.A.Bertrand,
C.Arrigoni,
G.Thiel,
A.Moroni.
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ABSTRACT
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dually
activated by hyperpolarization and binding of cAMP to their cyclic nucleotide
binding domain (CNBD). HCN isoforms respond differently to cAMP; binding of cAMP
shifts activation of HCN2 and HCN4 by 17 mV but shifts that of HCN1 by only 2-4
mV. To explain the peculiarity of HCN1, we solved the crystal structures and
performed a biochemical-biophysical characterization of the C-terminal domain
(C-linker plus CNBD) of the three isoforms. Our main finding is that
tetramerization of the C-terminal domain of HCN1 occurs at basal cAMP
concentrations, whereas those of HCN2 and HCN4 require cAMP saturating levels.
Therefore, HCN1 responds less markedly than HCN2 and HCN4 to cAMP increase
because its CNBD is already partly tetrameric. This is confirmed by voltage
clamp experiments showing that the right-shifted position of V(½) in
HCN1 is correlated with its propensity to tetramerize in vitro. These data
underscore that ligand-induced CNBD tetramerization removes tonic inhibition
from the pore of HCN channels.
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Links
