Molecular characteristics of recombinant human CD4 as deduced from polymorphic crystals

Peter D. Kwong, Seong Eon Ryu, Wayne A. Hendrickson, Richard Axel, Robert M. Sweet, Gail Folena-Wasserman, Preston Hensley, Raymond W. Sweet

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

We have grown crystals of a soluble recombinant form of human CD4, a transmembrane glycoprotein found predominantly on the surface of helper T cells. Crystals composed of the entire extracellular portion of CD4 exhibit extensive polymorphism. Of the five crystal types that have been grown, the best diffracts to Bragg spacings of 4.9 Å. Symmetry considerations and characterization of the asymmetric unit by volume-specific amino acid analysis lead to the suggestion that a tetramer is the fundamental unit of crystallization. The characterization also showed that several of the crystal types have unusually high solvent contents. Because high solvent content and weak diffraction are indicative of an extended flexible structure, we examined the molecular shape of the recombinant CD4 with ultracentrifugation and found that it has an axial ratio of roughly 6, when modeled as a prolate ellipsoid. These results, combined with crystal packing constraints, suggest dimensions of approximately 25 × 25 × 125 Å for a monomer. The structural features deduced here may be relevant to the biological function of CD4 as a receptor mediating cell-cell and cell-virus interactions.

Original languageEnglish
Pages (from-to)6423-6427
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number16
DOIs
StatePublished - 1990 Aug

Keywords

  • AIDS
  • Crystallization
  • Immune recognition
  • Molecular shape
  • Signal transduction

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