Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2007

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD.

Résumé

We engineered a class of proteins that binds selected polypeptides with high specificity and affinity. Use of the protein scaffold of Sac7d, belonging to a protein family that binds various ligands, overcomes limitations inherent in the use of antibodies as intracellular inhibitors: it lacks disulfide bridges, is small and stable, and can be produced in large amounts. An in vitro combinatorial/selection approach generated specific, high-affinity (up to 140 pM) binders against bacterial outer membrane secretin PulD. When exported to the Escherichia coli periplasm, they inhibited PulD oligomerization, thereby blocking the type II secretion pathway of which PulD is part. Thus, high-affinity inhibitors of protein function can be derived from Sac7d and can be exported to, and function in, a cell compartment other than that in which they are produced.

Dates et versions

hal-00412884 , version 1 (02-09-2009)

Identifiants

  • HAL Id : hal-00412884 , version 1
  • PUBMEDCENTRAL : PMC2084283

Citer

B. Mouratou, F. Schaeffer, I. Guilvout, D. Tello-Manigne, Anthony Paul Pugsley, et al.. Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD.. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (46), pp.17983-8. ⟨hal-00412884⟩

Collections

102 Consultations
0 Téléchargements

Partager

  • More