Mutation of a basic sequence in the laminin α2LG3 module leads to a lack of proteolytic processing and has different effects on β1 integrin-mediated cell adhesion and α-dystroglycan binding

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Abstract
A RRKRRQ sequence unique to the LG3 module of the laminin α2 chain was previously shown to be sensitive to endogenous proteolysis during the recombinant production of the tandem array α2LG1-3. Mutation of RQ surrounding the cleaved peptide bond did not prevent this processing and intracellular degradation. Alanine mutagenesis of three alternate basic residues, however, was shown to prevent the cleavage in α2LG1-3, allowing for the α2LG3 module to be obtained as a folded, globular fragment. The mutation did not change heparin and sulfatide binding or cell adhesion of α2LG1-3 which can be mediated by α3β1 and α6β1 integrins. It did, however, cause a 10-fold reduction in α-dystroglycan binding. The data favor the interpretation that binding epitopes for heparin/sulfatides, β1 integrins and α-dystroglycan occupy different parts of the α2LG1-3 structure