Kirsten Frank M, Dyda Fred, Dobrodumov Anatoliy, Gronenborn Angela M
Laboratories of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Struct Biol. 2002 Nov;9(11):877-85. doi: 10.1038/nsb854.
The structure of a mutant immunoglobulin-binding B1 domain of streptococcal protein G (GB1), which comprises five conservative changes in hydrophobic core residues, was determined by NMR spectroscopy and X-ray crystallography. The oligomeric state and quaternary structure of the mutant protein are drastically changed from the wild type protein. The mutant structure consists of a symmetric tetramer, with intermolecular strand exchange involving all four units. Four of the five secondary structure elements present in the monomeric wild type GB1 structure are retained in the tetrameric structure, although their intra- and intermolecular interactions are altered. Our results demonstrate that through the acquisition of a moderate number of pivotal point mutations, proteins such as GB1 are able to undergo drastic structural changes, overcoming reduced stability of the monomeric unit by multimerization. The present structure is an illustrative example of how proteins exploit the breadth of conformational space.
通过核磁共振光谱法和X射线晶体学确定了链球菌蛋白G（GB1）的突变免疫球蛋白结合B1结构域的结构，该结构域在疏水核心残基上有五个保守变化。突变蛋白的寡聚状态和四级结构与野生型蛋白相比发生了巨大变化。突变结构由对称四聚体组成，分子间链交换涉及所有四个单元。单体野生型GB1结构中存在的五个二级结构元件中的四个保留在四聚体结构中，尽管它们的分子内和分子间相互作用发生了改变。我们的结果表明，通过获得适度数量的关键点突变，诸如GB1之类的蛋白质能够发生剧烈的结构变化，通过多聚化克服单体单元稳定性降低的问题。目前的结构是蛋白质如何利用构象空间广度的一个说明性例子。
