Inoguchi Noriko, Mizuno Nobuhiro, Baba Seiki, Kumasaka Takashi, Natarajan Chandrasekhar, Storz Jay F, Moriyama Hideaki
School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
Protein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, Sayo, Japan.
PLoS One. 2017 Mar 31;12(3):e0174921. doi: 10.1371/journal.pone.0174921. eCollection 2017.
Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant.
Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules.
The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.
原产于落基山脉高海拔地区的鹿鼠（白足鼠），相对于低地同种个体，其血红蛋白已进化出更高的氧结合亲和力。为阐明导致血红蛋白 - 氧亲和力进化增加的分子机制，解析了高地血红蛋白变体的晶体结构，并与先前报道的低地变体结构进行了比较。
高地血红蛋白产生了至少两种晶体类型，其最长轴分别为507 Å和230 Å。使用较小晶胞的晶体，以2.2 Å分辨率解析了结构。不对称单元包含两个四聚体血红蛋白分子。
分析表明，高地血红蛋白变体中的αPro50促进了αHis45与血红素之间的稳定相互作用，而在αHis50的低地变体中未观察到这种相互作用。αPro50突变还改变了α1β2/α2β1亚基间界面处原子接触的性质。这些结果证明了亚基间相互作用中改变亲和力的变化是如何由结构上较远位点的突变产生的。
