**5. Conclusions**

Our results show that LrtA from cyanobacteria, a member of the long HPF subfamily, shows a clear propensity to self-associate and has an apparent low conformational stability. The structure was predicted to be formed by two domains, one of which was well-folded, whereas the other was disordered. These conformational features, together with the presence of a relatively high number of charged residues, provide an overall structural plasticity.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1422-0067/19/7/1857/ s1, There are 14 figures, showing: the intensity curve of the methyl groups from the DOSY experiment at pH 8.0 and 500 mM NaCl (Figure S1); the spectroscopic characterization of LrtA by NMR at pH 8.0 and 500 mM NaCl and 20 ◦C (Figure S2); the 1D 1H-NMR spectrum of LrtA at pH 4.5 and 500 mM NaCl and 20 ◦C (Figure S3); far-UV CD spectra of LrtA at pH 4.5 at two different concentrations (Figure S4); the SDS-PAGE gel with the glutaraldehyde cross-linking results (Figure S5); the fluorescence lifetime at pH 8.0 and 500 mM NaCl of LrtA at 0.98 μM (in protomer units) (Figure S6); the thermal denaturations followed by fluorescence at different pH values (Figure S7); the chemical (urea and GdmCl) denaturations of LrtA followed by fluorescence and CD (Figure S8); the predictions of disorder probability along the sequence (Figure S9); several models of the LrtA structure as obtained from homology modeling (Figure S10); the spectroscopic characterization of LrtA by NMR at pH 6.9 and 500 mM NaCl at 15 ◦C (Figure S11); the secondary structure of the protein obtained in MD simulations (Figure S12); the titration of LrtA to yeast RNA (Figure S13); and the SDS-gel of purified LrtA (Figure S14).

**Author Contributions:** Conceptualization, L.M.C., P.S., A.C.-A., J.G.H.-C., B.R., and J.L.N.; Methodology, L.M.C., P.S., A.C.-A., J.G.H.-C., B.R., and J.L.N.; Software, B.R.; Investigation, L.M.C., P.S., A.C.-A., J.G.H.-C., B.R., and J.L.N.; Resources, F.J.F. and M.I.M.-P.; Writing—Original Draft Preparation, L.M.C., P.S., A.C.-A., J.G.H.-C., B.R., F.J.F., M.I.M.-P., J.G.d.l.T., and J.L.N.; Writing—Review and Editing, B.R., A.C.-A., and J.L.N.; Supervision, J.G.d.l.T. and J.L.N.

**Funding:** This research was funded by Spanish Ministry of Economy and Competitiveness (CTQ2015-64445-R (to J.L.N.), BIO2016-78020-R to A.C.A., FIS2014-52212-R to P.S. and BIO2016-75634-P (to M.I.M.-P. and F.J.F.), with Fondo Social Europeo (E.S.F.)). J.G.T. and J.G.H.-C. We also like to express our gratitude for support from Fundación Séneca (Comunidad Autónoma de la Región de Murcia) (19353/PI/14). B.R. acknowledges kind hospitality and use of computational resources in the European Magnetic Resonance Center (CERM), Sesto Fiorentino (Florence), Italy. L.M.C. thanks support from Universidad Miguel Hernandez for her sabbatical stay.

**Conflicts of Interest:** The authors declare no conflict of interest.
