Structure of the liganded T state of haemoglobin identifies the origin of cooperative oxygen binding

Abstract

A molecular description of haemoglobin's cooperative oxygen binding and release was founded on the X-ray crystal structures of the deoxy-T and oxy-R states^1–3. Since the R state's oxygen affinity is close to that of an isolated subunit, the crucial allosteric phenomena are (1) the reduced affinity of the T state and (2) the kinetic pathway between the two quaternary structures. To investigate these phenomena directly, we have determined at high resolution (d_min = 2.1 Å) the crystal structures of two liganded T-state haemoglobins. In the liganded T-state α subunit, both the tight packing of the haem and the intersubunit contacts inhibit a conformational change between the F helix and FG corner which would allow the haem to become planar and the iron to assume symmetrical R-like coordination. In the β subunit, by contrast, we find no strain on the proximal side, but the intersubunit contacts prevent the haem from tilting about an axis parallel to the F helix which would open up the binding site to oxygen. In both subunits, ligand binding in the T state induces structural changes towards the tertiary conformation of the R state.