Allosteric Intermediates Indicate R2 is the Liganded Hemoglobin end State

Hemoglobin has been a long-standing paradigm for understanding protein allostery. Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, α2β82CA82β and α2β82ND82β , are described at 2.3 angstrom and 2.6 angstrom resolution, respectively. Strikingly, these crosslinked hemoglobins assume intermediate conformations that lie between those of R and the controversial liganded hemoglobin state R2 rather than between R and T. Thus, these structures support only a T$\leftrightarrow $R$\leftrightarrow $R2 allosteric pathway and underscore the physiological importance of the R2 conformation.