A model for the sickle hemoglobin fiber using both mutation sites.
The standard molecular model of the fiber of the sickle hemoglobin (HbS: beta6 Glu-->Val) has been revised to allow both beta6 mutation sites to participate in intermolecular contacts, rather than only one beta6 site as previously thought, for four molecules per 14-molecule fiber cross section. This structure accurately predicts the copolymerization of hybridized mixtures of HbS with HbA or HbC (beta6 Glu-->Lys), which could not be reconciled with prior models in which only half the beta6 sites were required for assembly. This model suggests new contacts within the fiber and raises the question of whether these cross-linked double strands could possess added stability important in such processes as nucleation.
Roufberg
A
A
Department of Physics, Drexel University, Philadelphia, Pennsylvania 19104, USA.
Ferrone
F A
FA
D000465:Algorithms; D000755:Anemia, Sickle Cell / Q000097:blood; D003198:Computer Simulation; D006451:Hemoglobin, Sickle / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006456:Hemoglobinuria / Q000097:blood; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D014633:Valine / Q000737:chemistry
D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D014633:Valine