Israel

Israel is a unique phenomenon among the world's nations, as it is a country built on an ideology and a religion. The country has its origin in the times of the Bible, some 3000 years ago. The 'Jewish Temple' in the land of the Bible has been destroyed several times over and its inhabitants were sent to exile in neighboring countries, from where they emigrated worldwide, creating today's 'Jewish Diaspora'... [Introduction

G503 Is Obligatory for Coupling of Regulatory Domains in NCX Proteins

In multidomain proteins, interdomain linkers allow an efficient transfer of regulatory information, although it is unclear how the information encoded in the linker structure coins dynamic coupling. Allosteric regulation of NCX proteins involves Ca²⁺-driven tethering of regulatory CBD1 and CBD2 (through a salt bridge network) accompanied by alignment of CBDs and Ca²⁺ occlusion at the interface of the two CBDs. Here we investigated “alanine-walk” substitutions in the CBD1–CBD2 linker (501-HAGIFT-506) and found that among all linker residues, only G503 is obligatory for Ca²⁺-induced reorientations of CBDs and slow dissociation of occluded Ca²⁺. Moreover, swapping between positions A502 and G503 in the CBD1–CBD2 linker results in a complete loss of slow dissociation of occluded Ca²⁺, meaning that dynamic coupling of CBDs requires an exact pose of glycine at position 503. Therefore, accumulating data revealed that position 503 occupied by glycine is absolutely required for Ca²⁺-driven tethering of CBDs, which in turn limits the linker’s flexibility and, thus, restricts CBD movements. Because G503 is extremely well conserved in eukaryotic NCX proteins, the information encoded in G503 is essential for dynamic coupling of the two-domain CBD tandem and, thus, for propagation of the allosteric signal