PROTEIN MOTIFS .10. THE GTP-BINDING MOTIF - VARIATIONS ON A THEME

GTP binding proteins (G-proteins) have wide-ranging functions in biolo gy, being involved in cell proliferation, signal transduction, protein synthesis, and protein targeting. Common to their functioning is that they are active in the GTP-bound form and inactive in the GDP-bound f orm. The protein synthesis elongation factor EF-Tu was the first G-pro tein whose nucleotide binding domain was solved structurally by X-ray crystallography to yield a structural definition of the GDP-bound form , but a still increasing number of new structures of G-proteins are ap pearing in the literature, in both GDP and GTP bound forms. A common s tructural core for nucleotide binding is present in all these structur es, and this core has long been known to include common consensus sequ ence elements involved in binding of the nucleotide. Nevertheless, sub tle changes in the common sequences reflect functional differences. Th erefore, it becomes increasingly important to focus on how these diffe rences are reflected in the structures, and how these structural diffe rences are related to function. The aim of this review is to describe to what extent this structural motif for GDP/GTP binding is common to other known structures of this class of proteins. We first describe th e common structural core of the G-proteins. Next, examples are based o n information available on the Ras protein superfamily, the targeting protein ARF, elongation factors EF-Tn and EF-G, and the heterotrimeric G-proteins. Finally, we discuss the important structures of complexes between GTP binding proteins and their substrates that have appeared in the literature recently.