3r8b Citations

Molecular basis of a million-fold affinity maturation process in a protein-protein interaction.

Abstract

Protein engineering is becoming increasingly important for pharmaceutical applications where controlling the specificity and affinity of engineered proteins is required to create targeted protein therapeutics. Affinity increases of several thousand-fold are now routine for a variety of protein engineering approaches, and the structural and energetic bases of affinity maturation have been investigated in a number of such cases. Previously, a 3-million-fold affinity maturation process was achieved in a protein-protein interaction composed of a variant T-cell receptor fragment and a bacterial superantigen. Here, we present the molecular basis of this affinity increase. Using X-ray crystallography, shotgun reversion/replacement scanning mutagenesis, and computational analysis, we describe, in molecular detail, a process by which extrainterfacial regions of a protein complex can be rationally manipulated to significantly improve protein engineering outcomes.

Reviews - 3r8b mentioned but not cited (1)

Articles - 3r8b mentioned but not cited (2)

  1. Engineering a soluble high-affinity receptor domain that neutralizes staphylococcal enterotoxin C in rabbit models of disease. Mattis DM, Spaulding AR, Chuang-Smith ON, Sundberg EJ, Schlievert PM, Kranz DM. Protein Eng Des Sel 26 133-142 (2013)
  2. Molecular basis of a million-fold affinity maturation process in a protein-protein interaction. Bonsor DA, Postel S, Pierce BG, Wang N, Zhu P, Buonpane RA, Weng Z, Kranz DM, Sundberg EJ. J Mol Biol 411 321-328 (2011)


Reviews citing this publication (1)

  1. Computational design of protein-protein interactions. Schreiber G, Fleishman SJ. Curr Opin Struct Biol 23 903-910 (2013)

Articles citing this publication (3)

  1. Partner-aware prediction of interacting residues in protein-protein complexes from sequence data. Ahmad S, Ahmad S, Mizuguchi K. PLoS One 6 e29104 (2011)
  2. Characterization of the Staphylococcal enterotoxin A: Vβ receptor interaction using human receptor fragments engineered for high affinity. Sharma P, Postel S, Sundberg EJ, Kranz DM. Protein Eng Des Sel 26 781-789 (2013)
  3. Combining different design strategies for rational affinity maturation of the MICA-NKG2D interface. Henager SH, Hale MA, Maurice NJ, Dunnington EC, Swanson CJ, Peterson MJ, Ban JJ, Culpepper DJ, Davies LD, Sanders LK, McFarland BJ. Protein Sci 21 1396-1402 (2012)