Calmels, TP, Callebaut, I, Léger, I, P Durand, Bril, A, Mornon, JP and Souchet, M (1998), "Sequence and 3D structural relationships between mammalian Ras- and Rho-specific GTPase-activating proteins (GAPs): the cradle fold.", FEBS Lett, 426, 2: 205-11.
Abstract: An extensive study of both sequence
and recent 3D structural data concerning GTPase interacting domains
of Ras- and Rho-specific GTPase-activating proteins (GAPs) shows
that these two subfamilies share a same 3D scaffold and are thus
related to each other. This relationship has heretofore remained
undetected although these domains of similar size are both totally
alpha-helical and activate nearly structurally identical targets (Ras
and Rho proteins). In this report, sequence similarities correlated
to 3D structures of p120rasGAP and p50rhoGAP were detected using
the sensitive two-dimensional method hydrophobic cluster analysis
(HCA). These patterns were further extended to other members in each
subfamily and the geometry orientation of crucial arginines R789 in p120
and R282 in p50 and of important stabilizing residues like p120R903
and p50N391 was confirmed. This overall structural relationship is
centered on an invariant motif of three consecutive helices that
we suggest to name the 'cradle fold'. This observation opens new
perspectives to understand how small GTPases are specifically regulated.
