The FASEB Journal, Vol 9, 167-174, Copyright © 1995 by The Federation of American Societies for Experimental Biology

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The actin fold

W Kabsch and KC Holmes
Max-Planck-Institut fur medizinische Forschung, Abteilung Biophysik, Heidelberg, Germany.

X-ray structure analysis of actin and of the NH2-terminal domain of the heat-shock cognate protein Hsc70 has revealed an unexpected extensive structural similarity between these two molecules. Despite the absence of significant similarity of their amino acid sequences, both proteins share the same core architecture and a common nucleotide binding site resembling the structure of hexokinase. All three are ATPases or kinases and bind ATP in association with Mg2+ or Ca2+. The common fold consists of two alpha/beta domains, which are connected by a putative hinge with an ATP-binding site situated between the domains. Each domain contains a five-stranded beta-sheet of identical topology, which suggests that the molecules may have evolved by gene duplication. From a comparison of the three aligned structures, a fingerprint sequence of the adenine nucleotide binding pocket was derived, which predicted that members of the glycerol kinase family should also have a similar fold of their nucleotide binding domain. This was later confirmed when the X- ray structure was published. Data base search with a refined consensus sequence has retrieved other sugar kinases, as well as the prokaryotic cell cycle proteins FtsA, MreB, and StbA, and two Escherichia coli phosphatases. These proteins are predicted to possess a structure similar to actin in the common core region. As exemplified for actin, Hsc70, and glycerol kinase, the diversity of biological function is provided by the polymorphism of the loops joining the beta-strands and helices in the core region and by inserted domains that show high variability.

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