ja0616128_si_001.pdf (592.54 kB)
Retinol Modulates Site-Specific Mobility of Apo-Cellular Retinol-Binding Protein to Promote Ligand Binding
journal contribution
posted on 2006-08-02, 00:00 authored by Tanja Mittag, Lorella Franzoni, Davide Cavazzini, Brian Schaffhausen, Gian Luigi Rossi, Ulrich L. GüntherA 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.