α3β1 Adhesion to laminin-5 and invasin

Critical and differential role of integrin residues clustered at the boundary between α3 N-terminal repeats 2 and 3

Xi Ping Zhang, Wilma Puzon-McLaughlin, Atsushi Irie, Nicholas Kovach, Nicole L. Prokopishyn, Suzanne Laferté, Ken Ichi Takeuchi, Tsutomu Tsuji, Yoshikazu Takada

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Integrin/ligand interaction is a therapeutic target for many diseases. We previously reported that residues critical for ligand binding are clustered in N-terminal repeat 3 (in the predicted 2-3 loop) of α4, α5 and αIIb. Here we have localized residues critical for ligand binding in the α3 subunit of integrin α3β1 with distinct ligand specificity (laminin-5). We identified an α3 epitope common to several function-blocking anti-α3 antibodies at the boundary between repeats 1 and 2 (residues 75-80). We found that swapping the predicted 4-1 loop (residues 153-165) at the boundary between repeats 2 and 3 with the corresponding α4 sequence and mutating Thr- 162 and Gly-163 residues in this predicted loop block laminin-5 binding. Thr- 162 and Gly-163 and the antibody epitope are separated in the primary structure; however, they are close to each other in the proposed β-propeller model. Mutating residues recently reported to block (Tyr-186 and Trp-188) or enhance (Asp-122) laminin-5 binding to α3β1 [Krukonis, E.S., Dersch, P., Eble, J.A., and Isberg, R.R. (1998) J. Biol. Chem. 273, 31837-31843] did not affect laminin-5 binding under the assay conditions used. Thr-162 and Gly-163 are not critical for adhesion to invasin, indicating that laminin-5 and invasin may use different recognition mechanisms, and that mutation of Thr- 162 and Gly-163 does not drastically affect the integrity of α3β1. These results suggest that residues critical for ligand binding may be similarly (but not identically) located in repeat 3 of the α subunit regardless of ligand specificity.

Original languageEnglish
Pages (from-to)14424-14431
Number of pages8
JournalBiochemistry
Volume38
Issue number43
DOIs
Publication statusPublished - Oct 26 1999
Externally publishedYes

Fingerprint

Terminal Repeat Sequences
Integrins
Adhesion
Ligands
Epitopes
Blocking Antibodies
Antibodies
Propellers
kalinin
Anti-Idiotypic Antibodies
Assays
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Zhang, X. P., Puzon-McLaughlin, W., Irie, A., Kovach, N., Prokopishyn, N. L., Laferté, S., ... Takada, Y. (1999). α3β1 Adhesion to laminin-5 and invasin: Critical and differential role of integrin residues clustered at the boundary between α3 N-terminal repeats 2 and 3. Biochemistry, 38(43), 14424-14431. https://doi.org/10.1021/bi990323b

α3β1 Adhesion to laminin-5 and invasin : Critical and differential role of integrin residues clustered at the boundary between α3 N-terminal repeats 2 and 3. / Zhang, Xi Ping; Puzon-McLaughlin, Wilma; Irie, Atsushi; Kovach, Nicholas; Prokopishyn, Nicole L.; Laferté, Suzanne; Takeuchi, Ken Ichi; Tsuji, Tsutomu; Takada, Yoshikazu.

In: Biochemistry, Vol. 38, No. 43, 26.10.1999, p. 14424-14431.

Research output: Contribution to journalArticle

Zhang, XP, Puzon-McLaughlin, W, Irie, A, Kovach, N, Prokopishyn, NL, Laferté, S, Takeuchi, KI, Tsuji, T & Takada, Y 1999, 'α3β1 Adhesion to laminin-5 and invasin: Critical and differential role of integrin residues clustered at the boundary between α3 N-terminal repeats 2 and 3', Biochemistry, vol. 38, no. 43, pp. 14424-14431. https://doi.org/10.1021/bi990323b
Zhang, Xi Ping ; Puzon-McLaughlin, Wilma ; Irie, Atsushi ; Kovach, Nicholas ; Prokopishyn, Nicole L. ; Laferté, Suzanne ; Takeuchi, Ken Ichi ; Tsuji, Tsutomu ; Takada, Yoshikazu. / α3β1 Adhesion to laminin-5 and invasin : Critical and differential role of integrin residues clustered at the boundary between α3 N-terminal repeats 2 and 3. In: Biochemistry. 1999 ; Vol. 38, No. 43. pp. 14424-14431.
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AU - Irie, Atsushi

AU - Kovach, Nicholas

AU - Prokopishyn, Nicole L.

AU - Laferté, Suzanne

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AU - Tsuji, Tsutomu

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