Streptomyces lividans, crystal structure

The Shaker potassium channel did not yield crystals for the first potassium ion channel X-ray crystallographic structure. Rather, it was the prokaryote bacterium Streptomyces lividans, abbreviated as the KcsA K+ channel, that first produced crystals suitable for crystallography. This structure, published in 1998 by MacKinnon s group in Science magazine, was received with great praise from the scientific community. It was known at that time that the amino acid sequence of KcsA was similar to that of other K channels, including vertebrate and invertebrate voltage-dependent K (Kv) channels (such as the... 

The successful crystallization and structural determination of the constitutively open charmel of Streptomyces lividans (Doyle et al., 1998) represented a large step forward in the understanding of function and selectivity of ion channels. 

KcsA is a potassium channel protein from Streptomyces lividans that assembles as a tetramer.68 An X-ray diffraction study of a crystal defined the transmembrane and some extracellular portions of the structure but no structural information could be obtained for cytoplasmic domains. Since the protein assembles as a tetramer, when one spin label is present on each subunit, it is difficult to interpret the dipolar interactions because of the presence of adjacent... 

Figure 2.7 Cutaway stereoview of the X-ray crystal structure of the K+ channel of Streptomyces lividans. The upper and lower ends of the channel are regions of high negative charge density while the central portion comprises hydrophobic amino acid side chains. Positively charged regions are on the outer surface, while the spheres represent K+ ion positions. (Reproduced with permission from [2] MacKinnon).

Just as there are cation channels, there are also trans-membrane channels involved in the transport of biologically important anions such as Cl-. The crystal structure of the CIC chloride channel from Salmonella typhimurium was reported in 2002.3 Along with the determination of the Streptomyces lividans potassium channel structure, this work won a share of the 2003 Nobel prize in chemistry for Roderick MacKinnon (Howard Hughes Medical Institute, New York, USA). Chloride channels catalyse the flow of chloride across cell membranes and play a significant role in functions such as... 

A recent structure-based lead-finding strategy was used for Kvl.5 inhibitors. The pore-forming domain of Kvl. 5 exhibits 54% sequence homology with the bacterial K+ channel KcsA from Streptomyces lividans, for which a crystal structure of the... 

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