Publications [#113100] of Harold P. Erickson

Papers Published

1. CD Jun, CV Carman, SD Redick, M Shimaoka, HP Erickson, TA Springer, Ultrastructure and function of dimeric, soluble intercellular adhesion molecule-1 (ICAM-1)., The Journal of biological chemistry, United States, vol. 276 no. 31 (August, 2001), pp. 29019-27, ISSN 0021-9258
   (last updated on 2009/02/12)

   Abstract:
   Previous studies have demonstrated dimerization of intercellular adhesion molecule-1 (ICAM-1) on the cell surface and suggested a role for immunoglobulin superfamily domain 5 and/or the transmembrane domain in mediating such dimerization. Crystallization studies suggest that domain 1 may also mediate dimerization. ICAM-1 binds through domain 1 to the I domain of the integrin alpha(L)beta(2) (lymphocyte function-associated antigen 1). Soluble C-terminally dimerized ICAM-1 was made by replacing the transmembrane and cytoplasmic domains with an alpha-helical coiled coil. Electron microscopy revealed C-terminal dimers that were straight, slightly bent, and sometimes U-shaped. A small number of apparently closed ring-like dimers and W-shaped tetramers were found. To capture ICAM-1 dimerized at the crystallographically defined dimer interface in domain 1, cysteines were introduced into this interface. Several of these mutations resulted in the formation of soluble disulfide-bonded ICAM-1 dimers (domain 1 dimers). Combining a domain 1 cysteine mutation with the C-terminal dimers (domain 1/C-terminal dimers) resulted in significant amounts of both closed ring-like dimers and W-shaped tetramers. Surface plasmon resonance studies showed that all of the dimeric forms of ICAM-1 (domain 1, C-terminal, and domain 1/C-terminal dimers) bound similarly to the integrin alpha(L)beta(2) I domain, with affinities approximately 1.5--3-fold greater than that of monomeric ICAM-1. These studies demonstrate that ICAM-1 can form at least three different topologies and that dimerization at domain 1 does not interfere with binding in domain 1 to alpha(L)beta(2).

   Keywords:
   Amino Acid Substitution • Animals • Binding Sites • CHO Cells • Cell Line • Cricetinae • Crystallography, X-Ray • Cysteine • DNA, Complementary • Dimerization • Humans • Intercellular Adhesion Molecule-1 • Lymphocyte Function-Associated Antigen-1 • Microscopy, Electron • Models, Molecular • Mutagenesis, Site-Directed • Protein Conformation • Protein Structure, Secondary • Recombinant Proteins • Surface Plasmon Resonance • Surface Properties • Transfection • chemistry • chemistry* • genetics • physiology • ultrastructure • ultrastructure*