Dissociation of Haemoglobin Chesapeake into Subunits

Abstract

AMONG the large number of human haemoglobin variants of known structure, most are functionally normal. Haemoglobin Chesapeake (α₂ 92 Arg→Leu β₂) is the first one found in association with elevated whole blood oxygen affinity and familial erythrocytosis. By contrast with haemoglobin A, isolated haemoglobin Chesapeake displays a six-fold increase in oxygen affinity and a marked reduction in haem–haem interaction (Hill's coefficient n=1.3), but a normal Bohr effect². In the past two years, other variants with similar properties have been reported, but none has been studied as extensively as haemoglobin Chesapeake. These mutants provide considerable information relating the structure and function of haemoglobin, for their amino-acid substitutions are likely to be at sites crucial to the normal function of the molecule. It is of considerable interest that in four of these haemoglobins (Chesapeake, J-Capetown, Yakima and Kempsey), the substitutions are located in the area of contact between the α₁ and β₂ chains³. Three-dimensional models constructed from the X-ray crystallographic data of Perutz and associates indicate that, during oxygenation, there is considerable movement of the β chains relative to the α chains at this interface⁴. It is likely that the symmetrical dissociation of oxyhaemoglobin into αβ dimers also occurs at the α₁β₂ contact areas^5,6.