Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Department of Applied Chemistry, College of Life Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan.
J Phys Chem Lett. 2023 Apr 27;14(16):3898-3906. doi: 10.1021/acs.jpclett.3c00258. Epub 2023 Apr 24.
Protein denaturation is a ubiquitous process that occurs both and . While our molecular understanding of the denatured structures of proteins is limited, it is commonly accepted that the loss of unique intramolecular contacts makes proteins larger. Herein, we report compaction of the immunoglobulin G1 (IgG1) protein upon acid denaturation. Small-angle X-ray scattering coupled with size exclusion chromatography revealed that IgG1 radii of gyration at pH 2 were ∼75% of those at a neutral pH. Scattering profiles showed a compact globular shape, supported by analytical ultracentrifugation. The acid denaturation of proteins with a decrease in size is energetically costly, and acid-induced compaction requires an attractive force for domain reorientation. Such intramolecular aggregation may be widespread in immunoglobulin proteins as noncanonical structures. Herein, we discuss the potential biological significance of these noncanonical structures of antibodies.
蛋白质变性是一种普遍存在的过程，既发生在生理条件下，也发生在非正常条件下。虽然我们对蛋白质变性结构的分子理解有限，但普遍认为，独特的分子内接触的丧失使蛋白质变得更大。在这里，我们报告了免疫球蛋白 G1（IgG1）在酸变性时的紧凑化。小角度 X 射线散射与尺寸排阻色谱法相结合表明，在 pH 值为 2 时 IgG1 的回转半径约为中性 pH 值时的 75%。散射谱图显示出紧凑的球形形状，这得到了分析超速离心的支持。蛋白质在尺寸减小的情况下发生变性是能量消耗大的，而酸诱导的紧凑化需要一种用于结构域重排的吸引力。这种分子内聚集在免疫球蛋白蛋白中可能很普遍，因为它们是非典型结构。在此，我们讨论了这些抗体的非典型结构的潜在生物学意义。
