The N-terminal region and the mid-region complex of the integrin beta 2 subunit

Suet Mien Tan, M K Robinson, K Drbal, Y van Kooyk, J M Shaw, S K Law

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In the primary sequence of the integrin beta subunit, the N-terminal region (NTR) and mid-region are separated by the I-like domain. To determine the spatial relationship and functional properties of the integrin beta(2) NTR and mid-region, we constructed beta(2)/beta(7) chimeras in which the NTR, I-like domain, and the mid-region of the beta(2) subunit were replaced by those of beta(7). Changing either the beta(2) NTR or mid-region, but not the I-like domain to that of beta(7) did not affect LFA-1 (alpha(L)beta(2)) formation and surface expression. Thus, the specificity of alpha(L)beta(2) pairing is conferred by the I-like domain but not the NTR or mid-region. Using these chimeras, the epitopes of six anti-beta(2) mAbs (H52, 7E4, AZN-L18, AZN-L27, KIM202, and MEM-148) were mapped. All except H52 require both the NTR and mid-region for epitope expression. Since these mAbs have distinct properties in terms of epitope expression and effect on LFA-1 binding to ICAM-1, we conclude that the beta(2) NTR and mid-region interact extensively. Although the I-like domain is located between the NTR and mid-region, its removal does not affect the folding of the beta(2) NTR/mid-region complex because this complex alone can be expressed as a soluble protein and precipitated by the appropriate mAbs. Finally, the mAbs H52 and 7E4, abrogated KIM185- but not Mg/EGTAinduced LFA-1/ICAM-1 binding and the epitope of MEM-148 is expressed on Mg/EGTA-activated but not resting LFA-1. These results suggest that the NTR/mid-region complex is involved in the regulation of LFA-1 function.

Original languageEnglish
Pages (from-to)36370-6
Number of pages7
JournalJournal of Biological Chemistry
Issue number39
Publication statusPublished - 28 Sept 2001


  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal/chemistry
  • CD18 Antigens/chemistry
  • COS Cells
  • Cell Adhesion
  • DNA, Complementary/metabolism
  • Epitopes
  • Flow Cytometry
  • Gene Library
  • Humans
  • Intercellular Adhesion Molecule-1/metabolism
  • Lymphocyte Function-Associated Antigen-1/metabolism
  • Molecular Sequence Data
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Transfection

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