Intermolecular contacts within sickle hemoglobin fibers

Stanley J. Watowich, Leon J. Gross, Robert Josephs

Research output: Contribution to journalConference article

Abstract

We have combined x-ray crystallographic coordinates of sickle hemoglobin (HbS) molecules with electron microscopic 3-D reconstruction data of HbS fibers to calculate residues involved in intermolecular contacts within the clinically relevant HbS fiber. The model accounts for the action of 80% of the fifty five point mutations of HbS whose effect on fiber formation has been studied. For instance, fiber formation is affected by thirty-three mutants. Of these mutants, thirty-one occur at the calculated intermolecular contact sites. Fiber formation is not affected by 28 known HbS mutants; 16 of these mutations occur at residues not involved in intermolecular contacts. The 12 mutations that occur at contact sites are postulated to not significantly increase fiber formation energy. The number of intermolecular contacts decreases with radius until, at the periphery of the particle there are no contacts. We suggest that this observation accounts for the limited radial growth of the particle and that a similar mechanism may be a factor in limiting the size of other helical particles.

Original languageEnglish (US)
Pages (from-to)316-323
Number of pages8
JournalProceedings of SPIE - The International Society for Optical Engineering
Volume1396
StatePublished - Jan 1 1991
EventApplications of Optical Engineering: Proceedings of OE/Midwest '90 - Rosemont, IL, USA
Duration: Sep 27 1990Sep 28 1990

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ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering

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