Structural basis for cooperative oxygen binding and bracelet-assisted assembly of Lumbricus terrestris hemoglobin
Wei-Ting Chen1,3*, Yu-Chuen Chen3, Horng-Huei Liou4, Chih-Yu Chao1,2,3
1Department of Physics, National Taiwan University, Taipei, Taiwan
2Graduate Institute of Applied Physics, National Taiwan University, Taipei, Taiwan
3Biomedical & Molecular Imaging Center, National Taiwan University, Taipei, Taiwan
4Division of Neurology, National Taiwan University Hospital, Taipei, Taiwan
* presenting author:Wei-Ting Chen, email:wtchen.phys.ntu@gmail.com
The iron-containing hemoglobins (Hbs) are essential proteins to serve as oxygen transporters in the blood. Among various kinds of Hbs, the earthworm Hbs are the champions in carrying oxygen due to not only their large size but also the unusually high cooperativity of ligand binding. However, the cooperative oxygen binding mechanisms are still mostly unknown. Here we report the cryo-electron microscopy structure of Lumbricus terrestris Hb in its native, oxygenated state at 9.1 Å resolution, showing remarkable differences from the carbon monoxide-binding X-ray structure. Our structural analysis first indicates that the cooperative ligand binding of L. terrestris Hb requires tertiary and quaternary transitions in the heme pocket and a global subunit movement facilitated by intra-ring and inter-ring contacts. Moreover, the additional sinusoidal bracelet provides the confirmation for the long-standing debate about the additional electron densities absent in the X-ray crystal structure.


Keywords: Hemoglobin, Cryo-EM, Allosteric cooperativity