Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca2+ channels.
Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca2+ channels.
复制标题
电压门控 Ca2 通道中离子选择和传导中的非谷氨酸孔残基。
DOI：
10.1016/s0006-3495(99)77092-x
复制
发表时间：
1999
影响因子：
3.4
通讯作者：
Sather,WA
中科院分区：
文献类型：
--
作者：
Williamson,AV;Sather,WA
High-affinity, intrapore binding of Ca2+over competing ions is the essential feature in the ion selectivity mechanism of voltage-gated Ca2+channels. At the same time, several million Ca2+ions can travel each second through the pore of a single open Ca2+channel. How such high Ca2+flux is achieved in the face of tight Ca2+binding is a current area of inquiry, particularly from a structural point of view. The ion selectivity locus comprises four glutamate residues within the channel's pore. These glutamates make unequal contributions to Ca2+binding, underscoring a role for neighboring residues in pore function. By comparing two Ca2+channels (the L-typeα1C, and the non-L-typeα1A) that differ in their pore properties but only differ at a single amino acid position near the selectivity locus, we have identified the amino-terminal neighbor of the glutamate residue in motif III as a determinant of pore function. This position is more important in the function ofα1Cchannels than inα1Achannels. For a systematic series of mutations at this pore position inα1C, both unitary Ba2+conductance and Cd2+block of Ba2+current varied with residue volume. Pore mutations designed to makeα1Cmore likeα1Aand vice versa revealed that relative selectivity for Ba2+over K+depended almost solely on pore sequence and not channel type. Analysis of thermodynamic mutant cycles indicates that the motif III neighbor normally interacts in a cooperative fashion with the locus, molding the functional behavior of the pore.
