TY - JOUR
T1 - The three-dimensional structure of sickle hemoglobin macrofibers.
AU - Bluemke, D. A.
AU - Carragher, B.
AU - Potel, M. J.
AU - Josephs, R.
PY - 1987
Y1 - 1987
N2 - The crystallization of deoxygenated sickle cell hemoglobin (HbS) at pH less than 6.5 is preceded by the formation of HbS macrofibers. In stirred solutions, macrofibers appear several hours after the formation of fibers and subsequently aggregate and crystallize. Like fibers, macrofibers are long helical structures consisting of alternating narrow and wide regions. Macrofibers have a pitch of 10,000 A and a diameter averaging 500 A. Here we present a three-dimensional structural analysis of HbS macrofibers. Image reconstructions of these particles show that they consist of 5 antiparallel rows with 8, 11, 12, 11, and 8 double strands per row. Double strands in the outer two rows are asymmetrically disposed resulting in "notches" in opposite corners of the particle cross section. The notches produce characteristic features in electron micrographs of macrofibers. Fourier-filtered images of macrofibers have been produced which reveal their structure in considerable detail. Computed Fourier transforms of macrofibers exhibit spacings of 64 A, 185 A, and 53 A similar to those in the Wishner-Love crystal. A cross-correlation analysis between filtered macrofiber images and electron density projections of Wishner-Love double strands establishes that double strands in adjacent rows are antiparallel. This analysis also shows that the macrofiber rows are displaced axially by differing amounts depending on their distance from the helical axis. Using this data, we have computed a three-dimensional electron density model of the macrofiber based on atomic hemoglobin coordinates. This model reproduces in detail the many features revealed in Fourier-filtered macrofiber images.
AB - The crystallization of deoxygenated sickle cell hemoglobin (HbS) at pH less than 6.5 is preceded by the formation of HbS macrofibers. In stirred solutions, macrofibers appear several hours after the formation of fibers and subsequently aggregate and crystallize. Like fibers, macrofibers are long helical structures consisting of alternating narrow and wide regions. Macrofibers have a pitch of 10,000 A and a diameter averaging 500 A. Here we present a three-dimensional structural analysis of HbS macrofibers. Image reconstructions of these particles show that they consist of 5 antiparallel rows with 8, 11, 12, 11, and 8 double strands per row. Double strands in the outer two rows are asymmetrically disposed resulting in "notches" in opposite corners of the particle cross section. The notches produce characteristic features in electron micrographs of macrofibers. Fourier-filtered images of macrofibers have been produced which reveal their structure in considerable detail. Computed Fourier transforms of macrofibers exhibit spacings of 64 A, 185 A, and 53 A similar to those in the Wishner-Love crystal. A cross-correlation analysis between filtered macrofiber images and electron density projections of Wishner-Love double strands establishes that double strands in adjacent rows are antiparallel. This analysis also shows that the macrofiber rows are displaced axially by differing amounts depending on their distance from the helical axis. Using this data, we have computed a three-dimensional electron density model of the macrofiber based on atomic hemoglobin coordinates. This model reproduces in detail the many features revealed in Fourier-filtered macrofiber images.
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M3 - Article
C2 - 3615496
AN - SCOPUS:0023080802
SN - 0361-7742
VL - 240
SP - 31
EP - 46
JO - Progress in clinical and biological research
JF - Progress in clinical and biological research
ER -