Accommodation of insertions in helices: the mutation in hemoglobin Catonsville (Pro 37 alpha-Glu-Thr 38 alpha) generates a 3(10)-->alpha bulge.

Hemoglobin Catonsville is a mutation of human hemoglobin (an alpha 2 beta 2 tetramer) in which a glutamate residue is inserted into the first turn of a highly conserved 3(10) helix (the C helix) of each alpha subunit. In theory, amino acid insertions (or deletions) in protein helices can be accommodated via two distinct mechanisms. One, termed the register shift mechanism, preserves the geometry of the helix while requiring all of the residues on one flank of the insertion site to rotate by 100 degrees in the case of an alpha helix or by 120 degrees in the case of a 3(10) helix. The other, termed the bulge (or indentation) mechanism, distorts the local geometry of the helix but does not alter the helix register. High-resolution X-ray diffraction analysis of deoxyhemoglobin Catonsville shows that the inserted residue is accommodated as a bulge, demonstrating that this is a viable mechanism. (In contrast, no such evidence is yet available for the register shift mechanism.) More specifically, the insertion converts one turn of the C helix from 3(10) geometry to alpha helix-like geometry, raising the possibility that a common mechanism for accommodating insertions and deletions within helices may involve localized interconversions between 3(10), alpha, and pi helical structures.