近日，國(guó)際著名雜志PLoS One在線刊登了中科院昆明動(dòng)物研究所研究人員的最新研究成果“Retinoid-Binding Proteins: Similar Protein Architectures Bind Similar Ligands via Completely Different Ways，”,，文章中，研究者在視黃醇類物質(zhì)轉(zhuǎn)運(yùn)蛋白結(jié)合機(jī)制差異研究中獲進(jìn)展,。
在進(jìn)化過程中,，相似的蛋白結(jié)構(gòu)可以用完全不同的方式結(jié)合相同的配體。類維生素A轉(zhuǎn)運(yùn)蛋白就是一個(gè)很好的例子,。雖然他們結(jié)合相似的配體（視黃醇,，視黃酸），配體的結(jié)合機(jī)制卻差別很大：在同一個(gè)家族和細(xì)胞位置的蛋白中配體結(jié)合方向相同,；不同家族和細(xì)胞位置蛋白中配體結(jié)合方向相反,。
在FABP家族中，CRBPs和CRABPs的配體都是β紫羅酮環(huán)指向轉(zhuǎn)脂蛋白疏水桶的內(nèi)部,，而不飽和脂肪酸鏈指向溶液的方向,。而在RBP家族RBP和ERABP蛋白中，配體方向剛好相反,。結(jié)構(gòu)比對(duì)和序列比對(duì)發(fā)現(xiàn),，每個(gè)蛋白的配體連接位點(diǎn)非常保守。但是不同蛋白間配體結(jié)合位置發(fā)生了改變,，并且和配體連接的氨基酸在不同蛋白中都不保守,。
中科院昆明動(dòng)物研究所黃京飛課題組張玉茹博士和趙玉琦博士運(yùn)用生物信息學(xué)和分子動(dòng)力學(xué)模擬的方法，詳盡解釋了這種生物學(xué)現(xiàn)象并進(jìn)一步提出了類維生素A物質(zhì)在生物體內(nèi)可能的轉(zhuǎn)運(yùn)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.
