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Cellular retinaldehyde binding protein-different binding modes and micro-solvation patterns for high-affinity 9-cis- and 11-cis-retinal substrates. 2013

Rachel E Helbling, and Christin S Bolze, and Marcin Golczak, and Krzysztof Palczewski, and Achim Stocker, and Michele Cascella
Department of Chemistry and Biochemistry, University of Bern , Freiestrasse 3, 3012 Bern, Switzerland.

We use molecular dynamics (MD) simulations to determine the binding properties of different retinoid species to cellular retinaldehyde binding protein (CRALBP). The complexes formed by 9-cis-retinal or 11-cis-retinal bound to both the native protein and the R234W mutant, associated to Bothnia-retina dystrophy, are investigated. The presented studies are also complemented by analysis of the binding structures of the CRALBP/9-cis-retinol and CRALBP/9,13-dicis-retinal complexes. We find that the poor X-ray scattering properties of the polyene tail of the ligand in all wild-type complexes can be attributed to a high mobility of this region, which does not localize in a single binding conformation even at very low temperatures. Our simulations report a clear difference in the residual solvation pattern in CRALBP complexes with either 9-cis- or 9,13-dicis-retinal. The reported structures indicate that the microsolvation properties of the ligand are the key structural element triggering the very recently discovered isomerase activity of this protein. The binding geometries obtained by MD simulations are validated by calculation of the respective optical spectra by the ZINDO/S semiempirical method, which can reproduce with good qualitative agreement the different red-shifts of the first absorption band of the different complexes.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D012164 Retinal Diseases Diseases involving the RETINA. Disease, Retinal,Diseases, Retinal,Retinal Disease
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012172 Retinaldehyde A diterpene derived from the carotenoid VITAMIN A which functions as the active component of the visual cycle. It is the prosthetic group of RHODOPSIN (i.e., covalently bonded to ROD OPSIN as 11-cis-retinal). When stimulated by visible light, rhodopsin transforms this cis-isomer of retinal to the trans-isomer (11-trans-retinal). This transformation straightens-out the bend of the retinal molecule and causes a change in the shape of rhodopsin triggering the visual process. A series of energy-requiring enzyme-catalyzed reactions convert the 11-trans-retinal back to the cis-isomer. 11-trans-Retinal,3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-Nonatetraenal,Axerophthal,Retinal,Retinene,Retinyl Aldehydde,Vitamin A Aldehyde,all-trans-Retinal,11-cis-Retinal,11 cis Retinal,11 trans Retinal,Aldehydde, Retinyl,Aldehyde, Vitamin A,all trans Retinal
D015785 Eye Diseases, Hereditary Transmission of gene defects or chromosomal aberrations/abnormalities which are expressed in extreme variation in the structure or function of the eye. These may be evident at birth, but may be manifested later with progression of the disorder. Hereditary Eye Diseases,Eye Disease, Hereditary,Hereditary Eye Disease
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics

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