RESEARCH ARTICLE NMR Structure and Dynamics of the Resuscitation Promoting Factor RpfC Catalytic Domain

Mycobacterium tuberculosis latent infection is maintained for years with no clinical symp-toms and no adverse effects for the host. The mechanism through which dormantM. tuber-culosis resuscitates and enters the cell cycle leading to tuberculosis is attracting much interest. The RPF family of proteins has been found to be responsible for bacteria resuscita-tion and normal proliferation. This family of proteins inM. tuberculosis is composed by five homologues (named RpfA-E) and understanding their conformational, structural and func-tional peculiarities is crucial to the design of therapeutic strategies.Therefore, we report the structural and dynamics characterization of the catalytic domain of RpfC fromM. tubercolo-sis by combining Nuclear Magnetic Resonance, Circular Dichroism and Molecular Dynam-ics data. We also show how the formation of a disulfide bridge, highly conserved among the homologues, is likely to modulate the shape of the RpfC hydrophobic catalytic cleft. This might result in a protein function regulation via a “conformational editing ” through a disulfide bond formation