An extended RNA binding surface through arrayed S1 and KH domains in transcription factor NusA

The crystal structure of Thermotoga maritima NusA, a transcription factor i nvolved in pausing, termination, and antitermination processes, reveals a f our-domain, rod-shaped molecule. An N-terminal alpha/beta portion, a five-s tranded beta -barrel (S1 domain), and two K-homology (KH) modules create a continuous spine of positive electrostatic potential, suitable for nonspeci fic mRNA attraction. Homology models suggest how, in addition, specific mRN A regulatory sequences can be recognized by the S1 and KH motifs. An arrang ement of multiple S1 and KH domains mediated by highly conserved residues i s seen, creating an extended RNA binding surface, a paradigm for other prot eins with similar domain arrays. Structural and mutational analyses indicat e that the motifs cooperate, modulating strength and specificity of RNA bin ding.