Local Unfolding of Fatty Acid Binding Protein to Allow Ligand Entry for Binding.
Angew Chem Int Ed Engl
; 55(24): 6869-72, 2016 06 06.
Article
em En
| MEDLINE
| ID: mdl-27105780
ABSTRACT
Fatty acid binding proteins are responsible for the transportation of fatty acids in biology. Despite intensive studies, the molecular mechanism of fatty acid entry to and exit from the protein cavity is still unclear. Here a cap-closed variant of human intestinal fatty acid binding protein was generated by mutagenesis, in which the helical cap is locked to the ß-barrel by a disulfide linkage. Structure determination shows that this variant adopts a closed conformation, but still uptakes fatty acids. Stopped-flow experiments indicate that a rate-limiting step exists before the ligand association and this step corresponds to the conversion of the closed form to the open one. NMR relaxation dispersion and H-D exchange data demonstrate the presence of two excited states one is native-like, but the other adopts a locally unfolded structure. Local unfolding of helix 2 generates an opening for ligands to enter the protein cavity, and thus controls the ligand association rate.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article