Role of highly central residues of P-loop and it's flanking region in preserving the archetypal conformation of Walker A motif of diverse P-loop NTPases

Abstract

P-loop NTPases represent a large and highly diverse protein family that is involved in variety of cellular functions. Walker A motif forms a typical arched conformation, necessary to accommodate the phosphate moiety of the nucleoside tri (or di-) phosphate in Ploop NTPases. The feature that maintains the ancient architecture of P-loop is unidentified and uncharacterized. Here, using a well established global network parameter, closeness centrality, we identify that Walker A and its flanking regions (N- and C-terminal) have high density of globally connected residue positions. We find that closeness centrality of these residue positions are conserved across common structural core of diverse domains of P-loop NTPase fold. Our results suggest the potential role of globally connected residues in maintaining the local conformation of P-loop.

Figure 1

A) Ribbon diagram of typical architecture of P-loop (Red) with bound nucleotide molecule (stick) of Ras superfamily proteins [Ras (green), Rab (cyan), Rho (blue), Ran (yellow), and Arf (magenta)]; B) Ribbon diagrams of typical architecture of Ploop (red) in representatives of diverse P-loop containing NTPases. 4 letter words are the PDBID.

Figure 2

Bar graph showing distribution of high closeness residue positions in diverse set of P-loop NTPases (red bar). Walker A containing proteins that do not form P-loop are depicted in blue bar. High density of high closeness residue positions (star marked) shown around Walker A (W1-W8) and its flanking regions N terminal (N1-N5) and C terminal (C1-C5).