Figure 1

(A) Multiple sequence alignment of the cpRAS GTPase domains. The sequence of the canonical HRAS GTPase domain is included for comparison. The M residue with a red background is the actual N-terminus of the HRAS protein, the dashed red line indicates the peptide bond within HRAS disjoined so that it can be aligned with the cpRAS domain. The blue dashed line indicates a bond connecting the HRAS GTPase domain with an unstructured C-terminal tail. Strands and helices as experimentally determined for GDP-bound HRAS are indicated below the alignment. G1 to G5 above the alignment mark the five conserved GTPase signature motifs as defined in [5]. Species abbreviations: Aca – Acanthamoeba castellanii, Aqu – Amphimedon queenslandica, Bfl – Branchiostoma floridae, Cow – Capsaspora owczarzaki, Ddi – Dictyostelium discoideum, Hsa – Homo sapiens, Mbr – Monosiga brevicollis, Ngr – Naegleria gruberi, Spu – Strongylocentrotus purpuratus. For accession numbers of the protein sequences see Additional file 1. (B) Predicted tertiary structure of the cpRAS domain and its comparison with the canonical human HRAS GTPase domain and the circularly permuted GTPase domain of the Bacillus subtilis protein YlqF. Dashed arrows represent parts of the proteins located N- or C-terminally of the GTPase domain. The dashed line connecting the helix5 and strand1 in the cpRAS model indicates an expected loop between these two elements, although the precise structure of this part of the domain could not be modelled (see the text). The dashed line connecting the helix1 and strand2 in YlqF represents a putative loop that is missing from the solved structure. Secondary structure elements in cpRAS and YlqF are labelled according to the equivalent β-strands and α-helices (S1 to S6 and H1 to H5) in HRAS, although their actual position in the polypeptide chain is different. Colours of the spectrum (from violet blue to red) are assigned to consecutive parts of the structures starting from the N-terminus.