Division of Biophysics, Department of Physiology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Biochim Biophys Acta Gen Subj. 2020 Feb;1864(2):129335. doi: 10.1016/j.bbagen.2019.03.021. Epub 2019 Apr 2.
Human hemoglobin is an allosteric protein that exerts exquisite control over ligand binding through large-scale conformational changes. The two-state model without intermediates offers a simple qualitative description of the allosteric behavior of hemoglobin, as presented in textbooks. However, there is renewed interest in this topic due to recent experimental breakthroughs that show how hemoglobin actually undergoes conformational transitions in response to environmental changes.
I review the current understanding of hemoglobin structure-function relationships revealed by recent discoveries. A unique single crystal, in which three protein molecules are allowed to express a whole range of quaternary structures, helped to reveal the detailed transition pathway including various intermediate forms. I also discuss the potential of single-molecule techniques that are currently under examination.
New crystallographic approaches reveal that the hemoglobin allosteric transition involves population shifts in multiple quaternary conformers rather than a simple two-state switch, and that coexisting individual conformers may have disproportionate effects on the apparent O affinity of hemoglobin.
These approaches provide a further level of complexity on the textbook statement of hemoglobin allostery, highlighting the relevance of conformational distributions in controlling the function and regulation of allosteric proteins.
人血红蛋白是一种变构蛋白，通过大规模构象变化对配体结合进行精细控制。教科书中呈现的无中间态两态模型为血红蛋白的变构行为提供了简单的定性描述。然而，由于最近的实验突破表明血红蛋白实际上如何响应环境变化发生构象转变，人们对这个话题重新产生了兴趣。
我回顾了最近的发现揭示的血红蛋白结构-功能关系的现有理解。一个独特的单晶允许三个蛋白质分子表达整个范围的四级结构，有助于揭示详细的转变途径，包括各种中间形式。我还讨论了目前正在检查的单分子技术的潜力。
新的晶体学方法表明，血红蛋白变构转变涉及多个四级构象的群体转移，而不是简单的两态开关，并且共存的单个构象可能对血红蛋白的表观氧亲和力产生不成比例的影响。
这些方法在教科书中对血红蛋白变构的表述上提供了进一步的复杂性，强调了构象分布在控制变构蛋白功能和调节中的相关性。
