期刊
STRUCTURE
卷 19, 期 5, 页码 733-747出版社
CELL PRESS
DOI: 10.1016/j.str.2011.02.009
关键词
-
资金
- National Institutes of Health [RO1 GM 57001]
- Roy J. Carver Charitable Trust [01-224]
The neuronal voltage-dependent sodium channel (Na(v)1.2), essential for generation and propagation of action potentials, is regulated by calmodulin (CaM) binding to the IQ motif in its alpha subunit. A peptide (Na(v)1.2(IQp), KRKQEEVSAIVIQRAYRRYLLKQKVKK) representing the IQ motif had higher affinity for apo CaM than (Ca2+)(4)-CaM. Association was mediated solely by the C-domain of CaM. A solution structure (2KXW.pdb) of apo C-13,N-15-CaM C-domain bound to Na(v)1.2(IQp), was determined with NMR. The region of Na(v)1.2(IQp) bound to CaM was helical; R1902, an Na(v)1.2 residue implicated in familial autism, did not contact CaM. The apo C-domain of CaM in this complex shares features of the same domain bound to myosin V IQ motifs (2IX7) and bound to an SK channel peptide (1G4Y) that does not contain an IQ motif. Thermodynamic and structural studies of CaM-Na(v)1.2(IQp) interactions show that apo and (Ca2+)(4)-CaM adopt distinct conformations that both permit tight association with Na(v)1.2(IQp) during gating.
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