Ramaraj Thiruvarangan, Angel Thomas, Dratz Edward A, Jesaitis Algirdas J, Mumey Brendan
Department of Computer Science, Montana State University, Bozeman, MT 59717, USA.
Biochim Biophys Acta. 2012 Mar;1824(3):520-32. doi: 10.1016/j.bbapap.2011.12.007. Epub 2012 Jan 10.
The structures of protein antigen-antibody (Ag-Ab) interfaces contain information about how Ab recognize Ag as well as how Ag are folded to present surfaces for Ag recognition. As such, the Ab surface holds information about Ag folding that resides with the Ab-Ag interface residues and how they interact. In order to gain insight into the nature of such interactions, a data set comprised of 53 non-redundant 3D structures of Ag-Ab complexes was analyzed. We assessed the physical and biochemical features of the Ag-Ab interfaces and the degree to which favored interactions exist between amino acid residues on the corresponding interface surfaces. Amino acid compositional analysis of the interfaces confirmed the dominance of TYR in the Ab paratope-containing surface (PCS), with almost two fold greater abundance than any other residue. Additionally TYR had a much higher than expected presence in the PCS compared to the surface of the whole antibody (defined as the occurrence propensity), along with aromatics PHE, TRP, and to a lesser degree HIS and ILE. In the Ag epitope-containing surface (ECS), there were slightly increased occurrence propensities of TRP and TYR relative to the whole Ag surface, implying an increased significance over the compositionally most abundant LYS>ASN>GLU>ASP>ARG. This examination encompasses a large, diverse set of unique Ag-Ab crystal structures that help explain the biological range and specificity of Ag-Ab interactions. This analysis may also provide a measure of the significance of individual amino acid residues in phage display analysis of Ag binding.
蛋白质抗原-抗体（Ag-Ab）界面的结构包含有关抗体如何识别抗原以及抗原如何折叠以呈现用于抗原识别的表面的信息。因此，抗体表面保留着与抗原折叠有关的信息，这些信息存在于抗原-抗体界面残基以及它们之间的相互作用中。为了深入了解此类相互作用的本质，我们分析了一个由53个非冗余的抗原-抗体复合物三维结构组成的数据集。我们评估了抗原-抗体界面的物理和生化特征，以及相应界面表面上氨基酸残基之间存在有利相互作用的程度。界面的氨基酸组成分析证实，酪氨酸（TYR）在抗体互补决定区表面（PCS）中占主导地位，其丰度几乎是任何其他残基的两倍。此外，与整个抗体表面相比（定义为出现倾向），酪氨酸在PCS中的存在高于预期，苯丙氨酸（PHE）、色氨酸（TRP）以及程度稍低的组氨酸（HIS）和异亮氨酸（ILE）也是如此。在抗原表位含表面（ECS）中，色氨酸和酪氨酸的出现倾向相对于整个抗原表面略有增加，这意味着相对于组成上最丰富的赖氨酸（LYS）>天冬酰胺（ASN）>谷氨酸（GLU）>天冬氨酸（ASP）>精氨酸（ARG），其重要性增加。这项研究涵盖了大量多样的独特抗原-抗体晶体结构，有助于解释抗原-抗体相互作用的生物学范围和特异性。该分析还可以衡量单个氨基酸残基在噬菌体展示分析抗原结合中的重要性。
