Tension in haemoglobin revealed by Fe-His(F8) bond rupture in the fully liganded T-state.
In 1972, Perutz proposed that the low affinity of T-state haemoglobin is caused by tension in the bond between the iron and the proximal histidine, restraining the Fe from moving into the porphyrin plane on binding oxygen. This proposal has often been disputed. If such tension does exist, it will be manifest in the liganded T-state. Here we describe the structure of the fully liganded T-state cyanide complex of haemoglobin, in which the Fe-proximal histidine bond in the alpha-subunits, but not in the beta-subunits, is ruptured. This rupture uncouples the structural changes at the alpha-haem from those in the globin and the beta-haem, and demonstrates unequivocally the existence of tension and its transmission through this bond.
Paoli
M
M
Department of Chemistry, University of York, York, YO1 5DD, UK.
Dodson
G
G
Liddington
R C
RC
Wilkinson
A J
AJ
D001665:Binding Sites; D006418:Heme / Q000737:chemistry; D006441:Hemoglobin A / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D006639:Histidine; D006801:Humans; D007501:Iron; D046911:Macromolecular Substances; D008958:Models, Molecular; D010108:Oxyhemoglobins / Q000737:chemistry; D011166:Porphyrins; D011487:Protein Conformation
D006454:Hemoglobins; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D011166:Porphyrins; C011207:cyanhemoglobin; D006418:Heme; D006639:Histidine; D006441:Hemoglobin A; D007501:Iron