Retinoid-Binding Proteins: Similar Protein Architectures Bind Similar Ligands via Completely Different Ways

被引:23
|
作者
Zhang, Yu-Ru [1 ,2 ]
Zhao, Yu-Qi [1 ,2 ]
Huang, Jing-Fei [1 ,3 ]
机构
[1] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China
[2] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
[3] Chinese Univ Hongkong, Joint Res Ctr Bioresources & Human Dis Mech, Kunming Inst Zool, Kunming, Peoples R China
来源
PLOS ONE | 2012年 / 7卷 / 05期
关键词
ACID; COMPLEX; IDENTIFICATION; SUMMARIES; ALIGNMENT; RECEPTOR; DATABASE; FAMILY; PDBSUM; SITE;
D O I
10.1371/journal.pone.0036772
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP) and epididymal retinoic acid binding protein (ERABP) carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs) and cellular retinoic acid-binding proteins (CRABPs) carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. Methodology/Principal Findings: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. Conclusions/Significance: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.
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页数:8
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