Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif γ2III4

Ulrike Mayer, Ernst Pöschl, Donald R. Gerecke, D. Wolfe Wagman, Robert E. Burgeson, Rupert Timpl

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

High affinity nidogen binding of laminin-1 (chain composition α1β1γ1) has been previously mapped to a single EGF-like motif γ1III4 of its γ1 chain. Two more isoforms, laminin-5 (α3β3γ2) and laminin-7 (α3β2γ1), show low and high binding activity, respectively, indicating that the γ2 chain is of low affinity. This was confirmed by recombinant production of the homologous EGF-like motif γ2III4 of the γ2 chain, which has a 100,000-fold lower binding activity than γ1III4. The crucial heptapeptide binding sequence Asn-lle-Asp-Pro-Asn-Ala-Val of γ1III4 is modified in γ2III4 by replacing both the central Asn and Val by Ser. Changing these replacements to Asn and Val by site-directed mutagenesis enhanced the activity of γ2III4 to a level which was only 5-fold lower than that of γ1III4. Despite their high sequence identity (77%) motifs γ1III4 and γ2III4 were also shown to differ considerably in immunological epitopes. This indicates distinctly different functions for laminins which differ in the γ chain isoform.

Original languageEnglish (US)
Pages (from-to)129-132
Number of pages4
JournalFEBS Letters
Volume365
Issue number2-3
DOIs
StatePublished - May 29 1995
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Serine
Protein Isoforms
Mutagenesis
Laminin
Site-Directed Mutagenesis
Epitopes
Chemical analysis
nidogen
kalinin
laminin 1
laminin 7

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Cell Biology

Keywords

  • Basement membrane
  • Laminin γ2 chain
  • Nidogen binding
  • Site-directed mutagenesis

Cite this

Mayer, Ulrike ; Pöschl, Ernst ; Gerecke, Donald R. ; Wolfe Wagman, D. ; Burgeson, Robert E. ; Timpl, Rupert. / Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif γ2III4. In: FEBS Letters. 1995 ; Vol. 365, No. 2-3. pp. 129-132.
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Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif γ2III4. / Mayer, Ulrike; Pöschl, Ernst; Gerecke, Donald R.; Wolfe Wagman, D.; Burgeson, Robert E.; Timpl, Rupert.

In: FEBS Letters, Vol. 365, No. 2-3, 29.05.1995, p. 129-132.

Research output: Contribution to journalArticle

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T1 - Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif γ2III4

AU - Mayer, Ulrike

AU - Pöschl, Ernst

AU - Gerecke, Donald R.

AU - Wolfe Wagman, D.

AU - Burgeson, Robert E.

AU - Timpl, Rupert

PY - 1995/5/29

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N2 - High affinity nidogen binding of laminin-1 (chain composition α1β1γ1) has been previously mapped to a single EGF-like motif γ1III4 of its γ1 chain. Two more isoforms, laminin-5 (α3β3γ2) and laminin-7 (α3β2γ1), show low and high binding activity, respectively, indicating that the γ2 chain is of low affinity. This was confirmed by recombinant production of the homologous EGF-like motif γ2III4 of the γ2 chain, which has a 100,000-fold lower binding activity than γ1III4. The crucial heptapeptide binding sequence Asn-lle-Asp-Pro-Asn-Ala-Val of γ1III4 is modified in γ2III4 by replacing both the central Asn and Val by Ser. Changing these replacements to Asn and Val by site-directed mutagenesis enhanced the activity of γ2III4 to a level which was only 5-fold lower than that of γ1III4. Despite their high sequence identity (77%) motifs γ1III4 and γ2III4 were also shown to differ considerably in immunological epitopes. This indicates distinctly different functions for laminins which differ in the γ chain isoform.

AB - High affinity nidogen binding of laminin-1 (chain composition α1β1γ1) has been previously mapped to a single EGF-like motif γ1III4 of its γ1 chain. Two more isoforms, laminin-5 (α3β3γ2) and laminin-7 (α3β2γ1), show low and high binding activity, respectively, indicating that the γ2 chain is of low affinity. This was confirmed by recombinant production of the homologous EGF-like motif γ2III4 of the γ2 chain, which has a 100,000-fold lower binding activity than γ1III4. The crucial heptapeptide binding sequence Asn-lle-Asp-Pro-Asn-Ala-Val of γ1III4 is modified in γ2III4 by replacing both the central Asn and Val by Ser. Changing these replacements to Asn and Val by site-directed mutagenesis enhanced the activity of γ2III4 to a level which was only 5-fold lower than that of γ1III4. Despite their high sequence identity (77%) motifs γ1III4 and γ2III4 were also shown to differ considerably in immunological epitopes. This indicates distinctly different functions for laminins which differ in the γ chain isoform.

KW - Basement membrane

KW - Laminin γ2 chain

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