近日，国际著名杂志PLoS One在线刊登了中科院昆明动物研究所研究人员的最新研究成果“Retinoid-Binding Proteins: Similar Protein Architectures Bind Similar Ligands via Completely Different Ways，”，文章中，研究者在视黄醇类物质转运蛋白结合机制差异研究中获进展。
在进化过程中，相似的蛋白结构可以用完全不同的方式结合相同的配体。类维生素A转运蛋白就是一个很好的例子。虽然他们结合相似的配体（视黄醇，视黄酸），配体的结合机制却差别很大：在同一个家族和细胞位置的蛋白中配体结合方向相同；不同家族和细胞位置蛋白中配体结合方向相反。
在FABP家族中，CRBPs和CRABPs的配体都是β紫罗酮环指向转脂蛋白疏水桶的内部，而不饱和脂肪酸链指向溶液的方向。而在RBP家族RBP和ERABP蛋白中，配体方向刚好相反。结构比对和序列比对发现，每个蛋白的配体连接位点非常保守。但是不同蛋白间配体结合位置发生了改变，并且和配体连接的氨基酸在不同蛋白中都不保守。
中科院昆明动物研究所黄京飞课题组张玉茹博士和赵玉琦博士运用生物信息学和分子动力学模拟的方法，详尽解释了这种生物学现象并进一步提出了类维生素A物质在生物体内可能的转运模型。（生物谷Bioon.com）
doi:10.1371/journal.pone.0036772
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Retinoid-Binding Proteins: Similar Protein Architectures Bind Similar Ligands via Completely Different Ways
Yu-Ru Zhang1,2, Yu-Qi Zhao1,2, Jing-Fei Huang1,3*
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.
