Molecular mechanisms of signal transduction by PAS sensor proteins

Abstract

The modular nature of proteins containing PAS (Per‐ARNT‐Sim) or other sensor domains enables signaling networks to be diverse and poses an interesting question: how can sensor domains with largely conserved tertiary structures regulate effector domains with very diverse structures and functions? In the absence of high‐resolution structures of full‐length PAS proteins it is instructive to study the structures of isolated PAS sensor domains where a signaling event is recognized and transmitted. We present the structure of a heme‐PAS domain dimer from Bradyrhizobium japonicum (bjFixLH) in a new space group (P1) and at higher resolutions (1.5‐1.8 Å) than those previously obtained [Ayers RA and Moffat K (2008) Biochemistry 47, 12078‐86]. Interestingly, bjFixLH can form two different dimers in the same crystallization solution, where the monomers in one dimer are rotated ~175º relative to the second. This suggests that PAS monomers are plastic and that two quite distinct quaternary structures are closely similar in free energy. As in the light‐sensitive PAS domain YtvA‐LOV from Bacillus subtilis, bjFixLH undergoes signal‐induced quaternary structural changes where monomers rotate ~2º relative to each other. Signal‐induced quaternary structural changes accommodate the ability of PAS sensor domains to regulate a wide variety of effector domains since PAS and effector domains would not be required to interact with each other in a structure‐specific manner. Our results are relevant for the rational design of novel PAS signaling proteins [Möglich A, Ayers RA, and Moffat K (2009) J Mol Biol 385, 1433‐44].