The role of the CPNKEKEC sequence in the β2 subunit I domain in regulation of integrin αLβ2 (LFA-1)

Tetsuji Kamata, Kenneth Khiem Tieu, Takehiko Tarui, Wilma Puzon-McLaughlin, Nancy Hogg, Yoshikazu Takada

研究成果: Article査読

47 被引用数 (Scopus)

抄録

The αL I (inserted or interactive) domain of integrin αLβ2 undergoes conformational changes upon activation. Recent studies show that the isolated, activated αL I domain is sufficient for strong ligand binding, suggesting the β2 subunit to be only indirectly involved. It has been unclear whether the activity of the αL I domain is regulated by the β2 subunit. In this study, we demonstrate that swapping the disulfide-linked CPNKEKEC sequence (residues 169-176) in the β2 I domain with a corresponding β3 sequence, or mutating Lys174 to Thr, constitutively activates αLβ2 binding to ICAM-1. These mutants do not require Mn2+ for ICAM-1 binding and are insensitive to the inhibitory effect of Ca2+. We have also localized a component of the mAb 24 epitope (a reporter of β2 integrin activation) in the CPNKEKEC sequence. Glu173 and Glu175 of the β2 I domain are identified as critical for mAb 24 binding. Because the epitope is highly expressed upon β2 integrin activation, it is likely that the CPNKEKEC sequence is exposed or undergoes conformational changes upon activation. Deletion of the αL I domain did not eliminate the mAb 24 epitope. This confirms that the αL I domain is not critical for mAb 24 binding, and indicates that mAb 24 detects a change expressed in part in the β2 subunit I domain. These results suggest that the CPNKEKEC sequence of the β2 I domain is involved in regulating the αL I domain.

本文言語English
ページ(範囲)2296-2301
ページ数6
ジャーナルJournal of Immunology
168
5
DOI
出版ステータスPublished - 2002 3月 1
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

フィンガープリント

「The role of the CPNKEKEC sequence in the β2 subunit I domain in regulation of integrin αLβ2 (LFA-1)」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル