Structural insights into the cellular retinaldehyde-binding protein (CRALBP).
Cellular retinaldehyde-binding protein (CRALBP) is an essential protein in the human visual cycle without a known three-dimensional structure. Previous studies associate retinal pathologies to specific mutations in the CRALBP protein. Here we use homology modeling and molecular dynamics methods to investigate the structural mechanisms by which CRALBP functions in the visual cycle. We have constructed two conformations of CRALBP representing two states in the process of ligand association and dissociation. Notably, our homology models map the pathology-associated mutations either directly in or adjacent to the putative ligand-binding cavity. Furthermore, six novel residues have been identified to be crucial for the hinge movement of the lipid-exchange loop in CRALBP. We conclude that the binding and release of retinoid involve large conformational changes in the lipid-exchange loop at the entrance of the ligand-binding cavity.
Liu
Tianyun
T
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Jenwitheesuk
Ekachai
E
Teller
David C
DC
Samudrala
Ram
R
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D009154:Mutation; D011487:Protein Conformation; D012164:Retinal Diseases / Q000235:genetics; D012172:Retinaldehyde / Q000737:chemistry; D016415:Sequence Alignment; D040681:Structural Homology, Protein
C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D008024:Ligands; D008055:Lipids; D012172:Retinaldehyde