Structural basis of glycosaminoglycan modification and of heterotypic interactions of perlecan domain V

M V Friedrich, W Gohring, Matthias Mörgelin, A Brancaccio, G David, R Timpl

Research output: Contribution to journalArticlepeer-review


The C-terminal perlecan domain V of about 90 kDa consists of laminin-type G domain modules (LG) (25 kDa) and epidermal growth factor-like modules (EG) (4 kDa) in the tandem arrangement LG1-EG1-EG2-LG2-EG3-EG4-LG3. Several shorter fragments have been prepared by recombinant production in mammalian cells and used to map the single glycosaminoglycan (GAG) substitution site and the binding of several carbohydrate and protein ligands. This identified a Ser3511 residue located in a short link region between EG4 and LG3 as being involved in GAG attachment. Electron microscopy provided evidence that the same substitution exists in tissue forms of perlecan. Heparan sulphate attached to this site was shown to bind to the alpha1LG4 module of laminin-1, indicating a role in basement membrane assembly and cell-matrix interactions. This site is also close to an Asn-Asp bond which is readily cleaved by an endogenous protease that depends on the presence of Asp and the LG2 module. A weak heparin binding site was shown to include the EG2 module, which contains five basic residues. Binding to sulphatides and the alpha-dystroglycan receptor was much stronger and required at least two LG modules. However, single LG modules appear to be sufficient for the interaction with the laminin-nidogen complex, while EG3-4 and some flanking regions are apparently involved in fibulin-2 binding. These observations indicate that a complex modular structure is required for domain V in order to provide a rich repertoire of potential biological functions.
Original languageEnglish
Pages (from-to)259-270
JournalJournal of Molecular Biology
Issue number1
Publication statusPublished - 1999

Subject classification (UKÄ)

  • Infectious Medicine


  • basement membranes
  • greek small letter alpha-dystroglycan
  • carbohydrate ligands
  • recombinant production
  • site-directed mutagenesis


Dive into the research topics of 'Structural basis of glycosaminoglycan modification and of heterotypic interactions of perlecan domain V'. Together they form a unique fingerprint.

Cite this