Abstract
The first example of the premature termination of a polypeptide chain in man appears to be Hb McKees Rocks, beta145 Tyr leads to Term, discovered in polycythemic members of a Caucasian family. Point mutation has apparently occurred at the codon for Tyr beta145 from UAU to a "nonsense" codon, UAA or UAG, resulting in a shortened polypeptide chain with Lys 144 as its carboxyl-terminal amino acid. Evidence for this structural conclusion is the absence of tryptic peptide betaT-15 from "fingerprints" of the abnormal beta-chain, the finding of C-terminal Lys, and the similarity between the functional properties of this variant hemoglobin and those of des Tyr (145)-His(146)beta hemoglobin resulting from carboxypeptidase-A digestion of normal human hemoglobin. Hb McKees Rocks has markedly abnormal properties: its oxygen affinity is the highest of the human variants described to date; its Bohr effect is reduced; it is devoid of subunit cooperativity; and it is unaffected by 2,3-diphosphoglyceric acid. These properties are probably the consequences of decreased stability of the T quaternary conformation and are partially restored in the presence of the strong allosteric effector inositol hexaphosphate.