*Article* **The Cyanobacterial Ribosomal-Associated Protein LrtA from** *Synechocystis* **sp. PCC 6803 Is an Oligomeric Protein in Solution with Chameleonic Sequence Properties**

**Lellys M. Contreras 1,†, Paz Sevilla 2,3, Ana Cámara-Artigas 4, José G. Hernández-Cifre 5, Bruno Rizzuti 6,\*, Francisco J. Florencio 7, María Isabel Muro-Pastor 7, José García de la Torre <sup>5</sup> and José L. Neira 8,9,\*,†**


Received: 18 May 2018; Accepted: 20 June 2018; Published: 24 June 2018

**Abstract:** The LrtA protein of *Synechocystis* sp. PCC 6803 intervenes in cyanobacterial post-stress survival and in stabilizing 70S ribosomal particles. It belongs to the hibernating promoting factor (HPF) family of proteins, involved in protein synthesis. In this work, we studied the conformational preferences and stability of isolated LrtA in solution. At physiological conditions, as shown by hydrodynamic techniques, LrtA was involved in a self-association equilibrium. As indicated by Nuclear Magnetic Resonance (NMR), circular dichroism (CD) and fluorescence, the protein acquired a folded, native-like conformation between pH 6.0 and 9.0. However, that conformation was not very stable, as suggested by thermal and chemical denaturations followed by CD and fluorescence. Theoretical studies of its highly-charged sequence suggest that LrtA had a Janus sequence, with a context-dependent fold. Our modelling and molecular dynamics (MD) simulations indicate that the protein adopted the same fold observed in other members of the HPF family (β-α-β-β-β-α) at its N-terminal region (residues 1–100), whereas the C terminus (residues 100–197) appeared disordered and collapsed, supporting the overall percentage of overall secondary structure obtained by CD deconvolution. Then, LrtA has a chameleonic sequence and it is the first member of the HPF family involved in a self-association equilibrium, when isolated in solution.

**Keywords:** conformational plasticity; disordered protein; folding; ribosomal protein; spectroscopy; protein stability
