2KXW

Structure of the C-domain Fragment of apo Calmodulin Bound to the IQ motif of Nav1.2

2KXW の概要

• エントリーDOI: 10.2210/pdb2kxw/pdb
• 分子名称: Calmodulin, Sodium channel protein type 2 subunit alpha (2 entities in total)
• 機能のキーワード: action potential, amino acid motifs, animals, autism, biomolecular, brain chemistry, calcium-binding proteins, calmodulin, channel, glutamine, humans, ion channel gating, isoleucine, iq motif, metal transport, models, molecular, nav1.2, neuronal, peptides, protein binding, protein structure, sodium channels, tertiary, tyrosine, voltage-dependent, voltage gated, calcium-binding protein-metal transport complex, calcium-binding protein/metal transport
• 由来する生物種: Paramecium tetraurelia; 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: P04775
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11786.40

構造登録者

Feldkamp, M.D.,Yu, L.,Shea, M.A. (登録日: 2010-05-13, 公開日: 2011-04-13, 最終更新日: 2024-05-01)

主引用文献

Feldkamp, M.D.,Yu, L.,Shea, M.A.
Structural and Energetic Determinants of Apo Calmodulin Binding to the IQ Motif of the Na(V)1.2 Voltage-Dependent Sodium Channel.
Structure, 19:733-747, 2011

PubMed Abstract: 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 α subunit. A peptide (Na(v)1.2(IQp), KRKQEEVSAIVIQRAYRRYLLKQKVKK) representing the IQ motif had higher affinity for apo CaM than (Ca(2+))(4)-CaM. Association was mediated solely by the C-domain of CaM. A solution structure (2KXW.pdb) of apo (13)C,(15)N-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 (Ca(2+))(4)-CaM adopt distinct conformations that both permit tight association with Na(v)1.2(IQp) during gating.

PubMed: 21439835
DOI: 10.1016/j.str.2011.02.009

実験手法

SOLUTION NMR