Coupling ligand recognition to protein folding in an engineered variant of rabbit ileal lipid binding protein.
We have engineered a variant of the beta-clam shell protein ILBP which lacks the alpha-helical motif that caps the central binding cavity; the mutant protein is sufficiently destabilised that it is unfolded under physiological conditions, however, it unexpectedly binds its natural bile acid substrates with high affinity forming a native-like beta-sheet rich structure and demonstrating strong thermodynamic coupling between ligand binding and protein folding.
Kouvatsos
Nikolaos
N
Centre for Biomolecular Sciences, School of Chemistry, University of Nottingham, University Park, Nottingham, UKNG7 2RD.
Meldrum
Jill K
JK
Searle
Mark S
MS
Thomas
Neil R
NR
D000818:Animals; D001665:Binding Sites; D002793:Cholic Acids / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D029363:Organic Anion Transporters, Sodium-Dependent / Q000737:chemistry*; D011487:Protein Conformation; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D027981:Symporters / Q000737:chemistry*; D013696:Temperature
D002793:Cholic Acids; D008024:Ligands; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter