Biology subjects

Colletier, J.-P.

Publications and source records attributed to Colletier, J.-P..

2 recordsLinked to original sources

bioRxiv2018

Extreme Amyloid Polymorphism in Staphylococcus aureus Virulent PSMα Peptides

Members of the Staphylococcus aureus phenol-soluble modulin (PSM) peptide family are secreted as functional amyloids that serve diverse roles in pathogenicity and may be present as full-length peptides or as naturally occurring truncations. We recently showed that the activity of PSM3, the most toxic member, stems from the formation of cross- fibrils, which are at variance with the cross-{beta} fibrils linked with eukaryotic amyloid pathologies. Here, we show that PSM1 and PSM4, involved in biofilm structuring, form canonical cross-{beta} amyloid fibrils wherein {beta}-sheets tightly mate through steric zipper interfaces, conferring high stability. Contrastingly, a truncated PSM3 has antibacterial activity, forms reversible fibrils, and reveals two polymorphic and atypical {beta}-rich fibril architectures. These architectures are radically different from both the cross- fibrils formed by full-length PSM3, and from the canonical cross-{beta} fibrils. Our results point to structural plasticity being at the basis of the functional diversity exhibited by S. aureus PSMs.

biochemistry↗

bioRxiv2017

Slow conformational exchange and overall rocking motion in ubiquitin protein crystals

Proteins perform their functions in solution but their structures are most frequently studied inside crystals. Here we probe how the crystal packing alters microsecond dynamics, using solid-state NMR measurements and multi-microsecond MD simulations of different crystal forms of ubiquitin. In particular, NEar-Rotary-resonance Relaxation Dispersion (NERRD) experiments probe angular backbone motion, while Bloch-McConnell Relaxation Dispersion data report on fluctuations of the local electronic environment. These experiments and simulations reveal that the packing of the protein can significantly alter the thermodynamics and kinetics of local conformational exchange. Moreover, we report small-amplitude reorientational motion of protein molecules in the crystal lattice with a [~]3-5{degrees} amplitude on a tens-of-microseconds time scale in one of the crystals, but not in others. An intriguing possibility arises that overall motion is to some extent coupled to local dynamics. Our study highlights the importance of considering the packing when analyzing dynamics of crystalline proteins.

biophysics↗