Mayer U, Pöschl E, Gerecke D R, Wagman D W, Burgeson R E, Timpl R
Max-Planck-Institut für Biochemie, Martinsried, Germany.
FEBS Lett. 1995 May 29;365(2-3):129-32. doi: 10.1016/0014-5793(95)00438-f.
High affinity nidogen binding of laminin-1 (chain composition alpha 1 beta 1 gamma 1) has been previously mapped to a single EGF-like motif gamma 1III4 of its gamma 1 chain. Two more isoforms, laminin-5 (alpha 3 beta 3 gamma 2) and laminin-7 (alpha 3 beta 2 gamma 1), show low and high binding activity, respectively, indicating that the gamma 2 chain is of low affinity. This was confirmed by recombinant production of the homologous EGF-like motif gamma 2III4 of the gamma 2 chain, which has a 100,000-fold lower binding activity than gamma 1III4. The crucial heptapeptide binding sequence Asn-Ile-Asp-Pro-Asn-Ala-Val of gamma 1III4 is modified in gamma 2III4 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 gamma 2III4 to a level which was only 5-fold lower than that of gamma 1III4. Despite their high sequence identity (77%) motifs gamma 1III4 and gamma 2III4 were also shown to differ considerably in immunological epitopes. This indicates distinctly different functions for laminins which differ in the gamma chain isoform.
