Macrofiber structure and the dynamics of sickle cell hemoglobin crystallization

Michael J. Potel*, Thomas E. Wellems, Robert J. Vassar, Barry Deer, Robert Josephs

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Fibers of deoxyhemoglobin S undergo spontaneous crystallization by a mechanism involving a variety of intermediate structures. These intermediate structures, in common with the fiber and crystal, consist of Wishner-Love double strands of hemoglobin S molecules arranged in different configurations. The structure of one of the key intermediates linking the fiber and crystal, called a macrofiber, has been studied by a variety of analytical procedures. The results of the analysis indicate that the intermediates involved in the fiber to crystal transition have many common structural features. Fourier analysis of electron micrographs of macrofibers confirms that they are composed of Wishner-Love double strands of hemoglobin molecules. Electron micrographs of macrofiber cross-sections reveal that the arrangement of the double strands in macrofibers resembles that seen in micrographs of the a axis projection of the crystal. This orientation provides an end-on view of the double strands which appear as paired dumb-bell-like masses. The structural detail becomes progressively less distinct towards the edge of the particle due to twisting of the double strands about the particle axis. Serial sections of macrofibers confirm that these particles do indeed rotate about their axes. The twist of the particle is right handed and its average pitch is 10,000 Å. The effect of rotation on the appearance of macrofiber cross-sections 300 to 400 Å thick can be simulated by a 15 ° rotation of an a axis crystal projection. The relative polarity of the double strands in macrofibers and crystals can be determined easily by direct inspection of the micrographs. In both macrofibers and crystals they are in an anti-parallel array. On the basis of these observations we conclude that crystallization of macrofibers involves untwisting and alignment of the double strands.

Original languageEnglish (US)
Pages (from-to)819-839
Number of pages21
JournalJournal of Molecular Biology
Volume177
Issue number4
DOIs
StatePublished - Aug 25 1984

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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