Computer models of a new deoxy-sickle cell hemoglobin fiber based on x-ray diffraction data

• Published in: Biophysical journal 1992-06, Vol.61 (6), p.1638-1646
• Main Authors: Mu, X.Q., Fairchild, B.M.
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Anemia, Sickle Cell - blood; Biological and medical sciences; Computer Simulation; Erythrocytes - physiology; Fourier Analysis; Fundamental and applied biological sciences. Psychology; Hemoglobin, Sickle - chemistry; Hemoglobin, Sickle - metabolism; Hemoproteins; Humans; Metalloproteins; Models, Structural; Protein Conformation; Proteins; X-Ray Diffraction
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(92)81967-7

A new x-ray fiber diffraction pattern from deoxygenated sickle cell erythrocytes has been observed. It displays 14 layer lines with a 109 A periodicity compared with the 64 A periodicity of the "classic" sickle cell hemoglobin (HbS) fiber. These data and association energy calculations serve as a basis for computer model building. Systematic searches over four-dimensional parameter space yielded twelve protofilament models that satisfy the following constraints: (a) two HbS molecules be related by twofold screw symmetry with a translational repeat of 109 A; (b) at least one of the substituted residues in HbS, val beta 6, should participate in intermolecular contacts; and (c) the energy of intermolecular interaction be less than -24 kcal/mol. Each of the protofilament models is a zigzag mono-strand that stands in contrast to the double-stranded protofilament of the "classic" fiber. Fiber models were constructed with each of the 12 protofilament models, pseudo-hexagonally packed. Searches of variable packing parameters showed four fiber models with minimal protofilament association energies and minimal differences between calculated transforms and observed data. The R-factor was less than 0.24 for each of these four models. In three of the fiber models the protofilament association energy is between -(93 and 130) kcal, and in a fourth, the energy is -64 kcal. One protofilament model constituted three distinct fiber models of the lower energy class, and a second protofilament model packed with a higher association energy into a fourth fiber model. The selection of a unique fiber model from among these four cannot be made because of the limited available data.