Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel Na(V)1.2.
Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel Na(V)1.2.
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DOI：
10.1016/j.bpc.2017.02.006
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发表时间：
2017-05
影响因子：
3.8
通讯作者：
Shea MA
中科院分区：
文献类型：
--
作者：
Hovey L;Fowler CA;Mahling R;Lin Z;Miller MS;Marx DC;Yoder JB;Kim EH;Tefft KM;Waite BC;Feldkamp MD;Yu L;Shea MA
电压门控钠通道家族中的几个成员受钙调蛋白(CaM)和离子钙的调节。神经元电压门控钠通道NaV1.2含有钙耗竭和钙饱和CaM的结合位点。我们测定了大鼠NaV1.2 IQ基序[IQRAYRYLLK]与apo CaM(~3 nM)和(Ca~(2+))4-CaM(~85 nM)结合的平衡解离常数，表明apo CaM结合是ApoCaM的30倍。核磁共振研究表明，对于apo和(Ca~(2+))4-CaM，NaV1.2 IQ基序多肽(NaV1.2|QP)与CaM(CAMC)的C-结构域残基发生特异性接触。为了了解钙是如何触发CaM-IQ界面的构象变化的，我们确定了(Ca~(2+))2-CAMC与NaV1.2IQp结合的溶液结构(2M5E.pdb)。(Ca2+)2-CAMC相对于IQ基序的极性与apo CAMC-Nav1.2IQp(2KXW)中的相反，表明CAMC识别Nav1.2IQp中的嵌套、反平行位点。CaM的逆转可能需要在钙结合过程中从IQ基序瞬时释放，并促进CAMn的重新定位，从而允许与IQ基序附近的非IQ NaV1.2残基或辅助调节蛋白相互作用。
Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3 nM) and (Ca2+)4-CaM (~85 nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca2+)4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1.2|Qp) exclusively made contacts with C-domain residues of CaM (CaMC). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a solution structure (2M5E.pdb) of (Ca2+)2-CaMC bound to NaV1.2IQp. The polarity of (Ca2+)2-CaMC relative to the IQ motif was opposite to that seen in apo CaMC-Nav1.2IQp (2KXW), revealing that CaMC recognizes nested, anti-parallel sites in Nav1.2IQp. Reversal of CaM may require transient release from the IQ motif during calcium binding, and facilitate a re-orientation of CaMN allowing interactions with non-IQ NaV1.2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif.
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DOI：
10.1126/science.aad8266
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen Y;Clarke OB;Kim J;Stowe S;Kim YK;Assur Z;Cavalier M;Godoy-Ruiz R;von Alpen DC;Manzini C;Blaner WS;Frank J;Quadro L;Weber DJ;Shapiro L;Hendrickson WA;Mancia F
通讯作者：
Mancia F
影响因子：
4
作者：
Black, DJ;Tran, QK;Persechini, A
通讯作者：
Persechini, A
影响因子：
4.8
作者：
Chagot, Benjamin;Potet, Franck;Chazin, Walter J.
通讯作者：
Chazin, Walter J.
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
斑马鱼造血所需的钙调蛋白相互作用蛋白 IQCG 的功能和分子特征
影响因子：
16.6
作者：
Chen, Li-Ting;Liang, Wen-Xue;Chen, Sai-Juan
通讯作者：
Chen, Sai-Juan