Retinol Modulates Site-Specific Mobility of Apo-Cellular
Retinol-Binding Protein to Promote Ligand Binding
Tanja Mittag
Lorella Franzoni
Davide Cavazzini
Brian Schaffhausen
Gian Luigi Rossi
Ulrich L. Günther
10.1021/ja0616128.s001
https://acs.figshare.com/articles/journal_contribution/Retinol_Modulates_Site_Specific_Mobility_of_Apo_Cellular_Retinol_Binding_Protein_to_Promote_Ligand_Binding/3067429
A fundamental question in protein science is how the inherent dynamics of a protein influence
its function. If this function involves interactions with a ligand, the protein−ligand encounter has the potential
to modulate the protein dynamics. This study reveals how site-specific mobility can be modulated by the
ligand to facilitate high affinity binding. We have investigated the mechanism of retinol uptake by the cellular
retinol-binding protein type I (CRBP) using line shape analysis of NMR signals. The highly similar structures
of apo- and holo-CRBP exhibit closed conformations that seemingly offer no access to ligand, yet the
protein binds retinol rapidly and with high affinity. NMR line shape analysis reveals how protein dynamics
resolve this apparent paradox. An initial nonspecific encounter with the ligand induces the formation of
long-lived conformers in the portal region of CRBP suggesting a mechanism how retinol accesses the
cavity.
2006-08-02 00:00:00
Promote Ligand BindingA
protein dynamics
ligand
CRBP
NMR line shape analysis
retinol
line shape analysis