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bioRxiv · 10.1101/178459

NMR studies reveal that protein dynamics critically mediate aggregation of the well-folded and very soluble E. coli S1 ribosomal protein

Lu, Y.·Lim, L.·Song, J.
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Abstract

Unlike mammalian aging associated with many hallmarks, E. coli aging is only significantly characterized by protein aggregation, thus offering an excellent model for addressing the relationship between protein aggregation and aging. Here we characterized conformations, unfolding and dynamics of ribosomal protein S1 and its D3/D5 domains using NMR, CD and fluorescence spectroscopy. S1 is a 557-residue modular protein containing six S1 motifs. Paradoxically, while S1 is well-folded and very soluble in vitro, it was found in various lists of aggregated E. coli proteins. Our results decipher: 1) S1 has dynamic inter-domain interactions. Strikingly, S1 and its D3/D5 domains have significantly exposed hydrophobic patches characterized by irreversible unfolding. 2) Although D5 has significantly restricted backbone motion on ps-ns time scale, it has global s-ms conformational dynamics and particularly high \"global breathing\" motions. 3) D5 assumes the conserved {beta}-barrel fold but contains large hydrophobic patches at least dynamically accessible. Taken together, our study reveals that S1 could be prone to aggregation due to significant dynamics at two levels: inter-domain interactions and individual domains, which may even render buried hydrophobic patches/cores accessible for driving aggregation. This mechanism is most likely to operate in many proteins of E. coli and other organisms including human.

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Lu, Y., Lim, L., Song, J.. 2017-08-19. NMR studies reveal that protein dynamics critically mediate aggregation of the well-folded and very soluble E. coli S1 ribosomal protein. https://doi.org/10.1101/178459

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