THE T-TO-R TRANSFORMATION IN HEMOGLOBIN - A REEVALUATION

The relationship between the T, R, and R2 quaternary forms of hemoglob in is examined by computational experiments. Contrary to previous sugg estions, we propose that the R quaternary form may lie on the pathway from T to R2. This proposal is consistent with four independent observ ations. (i) Difference distance maps are used to identify those parts of the molecule that undergo conformational change upon oxygenation. T he simplest interpretation of these maps brackets R between T and R2. (ii) Linear interpolation from T to R2 passes through R. (iii) The wel l-known ''switch'' region (so called because, upon transition between the T and R quaternary forms, a residue from the beta 2 subunit toggle s between two stable positions within the alpha 1 subunit) progresses from T through R to R2, successively. (iv) A hitherto undocumented fea ture, diagnostic of the R structure, is noted within the cu subunit: u pon transformation from T to R, the p-turns at the amino termini of th e E and F helices flip from one turn type to another. Upon transformat ion from R to R2, the latter turn-a strained conformation-flips back a gain.