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, alpha2beta82CA82beta and alpha2beta82ND82beta, are described at 2.3 A and 2.6 A 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 left and right arrow R left and right arrow R2 allosteric pathway and underscore the physiological importance of the R2 conformation.
Schumacher
M A
MA
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Zheleznova
E E
EE
Poundstone
K S
KS
Kluger
R
R
Jones
R T
RT
Brennan
R G
RG
D000494:Allosteric Regulation; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011487:Protein Conformation
D006454:Hemoglobins; D008024:Ligands