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PDBsum entry 2mpf
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Transport protein
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PDB id
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2mpf
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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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Solution structure human hcn2 cnbd in the camp-unbound state
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Structure:
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Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2. Chain: a. Fragment: cyclic nucleotide binding domain (unp residues 521-672). Synonym: hcn2, brain cyclic nucleotide-gated channel 2, bcng-2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hcn2, bcng2. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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NMR struc:
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20 models
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Authors:
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A.Saponaro,S.R.Pauleta,F.Cantini,M.Matzapetakis,C.Hammann,L.Banci, G.Thiel,B.Santoro,A.Moroni
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Key ref:
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A.Saponaro
et al.
(2014).
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
Proc Natl Acad Sci U S A,
111,
14577-14582.
PubMed id:
DOI:
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Date:
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16-May-14
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Release date:
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03-Sep-14
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PROCHECK
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Headers
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References
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Q9UL51
(HCN2_HUMAN) -
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 from Homo sapiens
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Seq:
Struc:
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889 a.a.
139 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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DOI no:
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Proc Natl Acad Sci U S A
111:14577-14582
(2014)
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PubMed id:
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Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
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A.Saponaro,
S.R.Pauleta,
F.Cantini,
M.Matzapetakis,
C.Hammann,
C.Donadoni,
L.Hu,
G.Thiel,
L.Banci,
B.Santoro,
A.Moroni.
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ABSTRACT
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cAMP signaling in the brain mediates several higher order neural processes.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind
cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus
playing a unique role in brain function. Neuronal HCN channels are also
regulated by tetratricopeptide repeat-containing Rab8b interacting protein
(TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by
interacting with the channel CNBD. To unravel the molecular mechanisms
underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we
determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free
form and mapped on it the TRIP8b interaction site. We reconstruct here the full
conformational changes induced by cAMP binding to the HCN channel CNBD. Our
results show that TRIP8b does not compete with cAMP for the same binding region;
rather, it exerts its inhibitory action through an allosteric mechanism,
preventing the cAMP-induced conformational changes in the HCN channel CNBD.
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