MULTIPLE MOLECULAR RECOGNITION PROPERTIES OF THE LIPOCALIN PROTEIN FAMILY
MULTIPLE MOLECULAR RECOGNITION PROPERTIES OF THE LIPOCALIN PROTEIN FAMILY
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DOI：
10.1002/jmr.300080304
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发表时间：
1995-05-01
影响因子：
2.7
通讯作者：
FLOWER, DR
中科院分区：
文献类型：
--
作者：
FLOWER, DR
脂载蛋白是一类细胞外小配体结合蛋白，具有一系列不同的分子识别特性。虽然它们与小疏水分子的结合，以及在较小程度上与细胞表面受体的结合是众所周知的，但这里显示，大分子复合物的形成也是该家族的共同特征。对已知晶体结构的分析表明，脂钙蛋白具有保守的共同结构：具有重复+1拓扑结构的反平行β -桶。比较表明，在这种整体相似性中，单个蛋白质的结构特别适应于结合其特定的配体，从内部腔（在桶内）和/或外部环支架形成结合位点，这产生了不同的结合模式，反映了适应不同形状、大小和化学结构的配体的需要。脂质体折叠的结构表明，这个桶的两端和两侧在拓扑结构上是不同的，在结构和序列变异的分析中也有明显的差异。这些差异可能与实验证据有关，表明脂钙蛋白折叠两端之间可能存在功能二分法。分子结构不变的一端可能与普通细胞表面受体的一般结合有关，而更可变的一端则适应于结合小配体和通过暴露的结合表面形成大分子复合物的特殊任务。
The lipocalins, a diverse family of small extracellular ligand binding proteins, display a remarkable range of different molecular recognition properties. While their binding of small hydrophobic molecules, and to a lesser extent their binding to cell surface receptors, is well known, it is shown here that formation of macromolecular complexes is also a common feature of this family. Analysis of known crystallographic structures reveals that the lipocalins possess a conserved common structure: an antiparallel beta-barrel with a repeated +1 topology. Comparisons show that within this overall similarity the structure of individual proteins is specifically adapted to bind their particular ligands, forming a binding site from an internal cavity (within the barrel) and/or an external loop scaffold, which gives rise to different binding modes that reflects the need to accommodate ligands of different shape, size, and chemical structure. The architecture of the lipocalin fold suggests that both the ends and sides of this barrel are topologically distinct, differences also apparent in analyses of structural and sequence variation within the family. These differences can be linked to experimental evidence suggesting a possible functional dichotomy between the two ends of the lipocalin fold. The structurally invariant end of the molecule may be implicated in general binding to common cell surface receptors, while the more variable end is adapted to the specialised tasks of binding small ligands and forming macromolecular complexes via an exposed binding surface.