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The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding.

Publication ,  Journal Article
Takagi, J; DeBottis, DP; Erickson, HP; Springer, TA
Published in: Biochemistry
April 2, 2002

Integrin beta subunits contain a highly conserved I-like domain that is known to be important for ligand binding. Unlike integrin I domains, the I-like domain requires integrin alpha and beta subunit association for optimal folding. Pactolus is a novel gene product that is highly homologous to integrin beta subunits but lacks associating alpha subunits [Chen, Y., Garrison, S., Weis, J. J., and Weis, J. H. (1998) J. Biol. Chem. 273, 8711-8718] and a approximately 30 amino acid segment corresponding to the specificity-determining loop (SDL) in the I-like domain. We find that the SDL is responsible for the defects in integrin beta subunit expression and folding in the absence of alpha subunits. When transfected in the absence of alpha subunits into cells, extracellular domains of mutant beta subunits lacking SDL, but not wild-type beta subunits, were well secreted and contained immunoreactive I-like domains. The purified recombinant soluble beta1 subunit with the SDL deletion showed an elongated shape in electron microscopy, consistent with its structure in alphabeta complexes. The SDL segment is not required for formation of alpha5beta1, alpha4beta1, alphaVbeta3, and alpha6beta4 heterodimers, but is essential for fomation of alpha6beta1, alphaVbeta1, and alphaLbeta2 heterodimers, suggesting that usage of subunit interface residues is variable among integrins. The beta1 SDL is required for ligand binding and for the formation of the epitope for the alpha5 monoclonal antibody 16 that maps to loop segments connecting blades 2 and 3 of beta-propeller domain of alpha5, but is not essential for nearby beta-propeller epitopes.

Duke Scholars

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

April 2, 2002

Volume

41

Issue

13

Start / End Page

4339 / 4347

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Structure, Secondary
  • Protein Folding
  • Protein Binding
  • Precipitin Tests
  • Mutation
  • Molecular Sequence Data
 

Citation

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Takagi, J., DeBottis, D. P., Erickson, H. P., & Springer, T. A. (2002). The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding. Biochemistry, 41(13), 4339–4347. https://doi.org/10.1021/bi016047u
Takagi, Junichi, Daniel P. DeBottis, Harold P. Erickson, and Timothy A. Springer. “The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding.Biochemistry 41, no. 13 (April 2, 2002): 4339–47. https://doi.org/10.1021/bi016047u.
Takagi, Junichi, et al. “The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding.Biochemistry, vol. 41, no. 13, Apr. 2002, pp. 4339–47. Pubmed, doi:10.1021/bi016047u.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

April 2, 2002

Volume

41

Issue

13

Start / End Page

4339 / 4347

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Structure, Secondary
  • Protein Folding
  • Protein Binding
  • Precipitin Tests
  • Mutation
  • Molecular Sequence Data