Structural insights into the cellular retinaldehyde‐binding protein (CRALBP)

T Liu, E Jenwitheesuk, DC Teller… - PROTEINS: Structure …, 2005 - Wiley Online Library
T Liu, E Jenwitheesuk, DC Teller, R Samudrala
PROTEINS: Structure, Function, and Bioinformatics, 2005Wiley Online Library
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 …
Abstract
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. Proteins 2005. © 2005 Wiley‐Liss, Inc.
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