The top of the inserted-like domain of the integrin lymphocyte function-associated antigen-1 β subunit contacts the α subunit β-propeller domain near β-sheet 3

Qun Zang, Chafen Lu, Chichi Huang, Junichi Takagi, Timothy A. Springer

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29 Scopus citations

Abstract

We find that monoclonal antibody YTA-1 recognizes an epitope formed by a combination of the integrin α(L) and β2 subunits of LFA-1. Using human/mouse chimeras of the α(L) and β2 subunits, we determined that YTA-1 binds to the predicted inserted (I)-like domain of the β2 subunit and the predicted β-propeller domain of the α(L) subunit. Substitution into mouse LFA-1 of human residues Ser302 and Arg303 of the β2 subunit and Pro78, Thr79, Asp80, Ile365 and Asn367 of the α(L) subunit is sufficient to completely reconstitute YTA-1 reactivity. Antibodies that bind to epitopes that are nearby in models of the I-like and β-propeller domains compete with YTA-1 monoclonal antibody for binding. The predicted β-propeller domain of integrin α subunits contains seven β-sheets arranged like blades of a propeller around a pseudosymmetry axis. The antigenic residues cluster on the bottom of this domain in the 1-2 loop of blade 2, and on the side of the domain in β-strand 4 of blade 3. The I domain is inserted between these blades on the top of the β-propeller domain. The antigenic residues in the β subunit localize to the top of the I-like domain near the putative Mg2+ ion binding site. Thus, the I-like domain contacts the bottom or side of the β-propeller domain near β-sheets 2 and 3. YTA-1 preferentially reacts with activated LFA-1 and is a function-blocking antibody, suggesting that conformational movements occur near the interface it defines between the LFA-1 α and β subunits.

Original languageEnglish (US)
Pages (from-to)22202-22212
Number of pages11
JournalJournal of Biological Chemistry
Volume275
Issue number29
DOIs
StatePublished - Jul 21 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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