The βγ-Crystallin Superfamily Contains a Universal Motif for Binding Calcium,

The βγ-crystallin superfamily consists of evolutionarily related proteins with domain topology similar to lens β- and γ-crystallins, formed from duplicated Greek key motifs. Ca2+ binding was found in a few βγ-crystallin members earlier, although its prevalence and diversity as inherent molecular properties among members of the superfamily are not well studied. To increase our understanding of Ca2+ binding in various βγ-crystallins, we undertook comprehensive structural and Ca2+-binding studies of seven members of the superfamily from bacteria, archaea, and vertebrates, including determination of high-resolution crystal structures of three proteins. Our structural observations show that the determinants of Ca2+ coordination remain conserved in the form of an N/D-N/D-#-I-S/T-S motif in all domains. However, binding of Ca2+ elicits varied physicochemical responses, ranging from passive sequestration to active stabilization. The motif in this superfamily is modified in some members like lens crystallins where...