Macrofiber structure and the dynamics of sickle cell hemoglobin crystallization

Area of Science:

• Biophysics
• Molecular Biology
• Hematology

Background:

• Deoxyhemoglobin S fibers spontaneously crystallize through various intermediate structures.
• These structures, including macrofibers, share common features with the final crystal.

Purpose of the Study:

• To elucidate the structure of macrofibers, a key intermediate in deoxyhemoglobin S fiber crystallization.
• To understand the structural relationship between macrofibers and deoxyhemoglobin S crystals.

Main Methods:

• Analysis of macrofiber structure using various analytical procedures.
• Fourier analysis of electron micrographs.
• Examination of serial sections of macrofibers.
• Comparison of macrofiber cross-sections with crystal projections.

Main Results:

• Macrofibers are confirmed to be composed of Wishner-Love double strands of hemoglobin S molecules.
• The arrangement of double strands in macrofibers resembles the crystal's a-axis projection.
• Macrofibers exhibit a right-handed twist with an average pitch of 10,000 A.
• Double strands in both macrofibers and crystals are arranged in an anti-parallel array.

Conclusions:

• Intermediate structures in deoxyhemoglobin S crystallization share common structural features.
• Macrofiber crystallization involves untwisting and alignment of the double strands.
• The anti-parallel arrangement of double strands is conserved from macrofibers to crystals.