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An ester bond underlies the mechanical strength of a pathogen surface protein.

Hai LeiQuan MaWenfei LiJing WenHai-Bo MaMeng QinWei WangYi Cao
Published in: Nature communications (2021)
Gram-positive bacteria can resist large mechanical perturbations during their invasion and colonization by secreting various surface proteins with intramolecular isopeptide or ester bonds. Compared to isopeptide bonds, ester bonds are prone to hydrolysis. It remains elusive whether ester bonds can completely block mechanical extension similarly to isopeptide bonds, or whether ester bonds dissipate mechanical energy by bond rupture. Here, we show that an ester-bond containing stalk domain of Cpe0147 is inextensible even at forces > 2 nN. The ester bond locks the structure to a partially unfolded conformation, in which the ester bond remains largely water inaccessible. This allows the ester bond to withstand considerable mechanical forces and in turn prevent complete protein unfolding. However, the protecting effect might be reduced at non-physiological basic pHs or low calcium concentrations due to destabilizing the protein structures. Inspired by this design principle, we engineer a disulfide mutant resistant to mechanical unfolding under reducing conditions.
Keyphrases
  • transition metal
  • protein protein
  • high resolution
  • molecular dynamics simulations
  • candida albicans
  • single molecule
  • gram negative
  • visible light