title: Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan.
abstract: Nidogen and perlecan are large multifunctional basement membrane (BM) proteins conserved in all metazoa. Their high-affinity interaction, which is likely to contribute to BM assembly and function, is mediated by the central G2 domain in nidogen and the third immunoglobulin (IG)-like domain in perlecan, IG3. We have solved the crystal structure at 2.0 A resolution of the mouse nidogen-1 G2-perlecan IG3 complex. Perlecan IG3 belongs to the I-set of the IG superfamily and binds to the wall of the nidogen-1 G2 beta-barrel using beta-strands C, D and F. Nidogen-1 residues participating in the extensive interface are highly conserved, whereas the corresponding binding site on perlecan is more variable. We hypothesize that a second, as yet unidentified, activity of nidogen overlaps with perlecan binding and accounts for the unusually high degree of surface conservation in the G2 domain.
authors.affiliation: Biophysics Section, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BW, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kvansakul
authors.forename: M
authors.initials: M
authors.lastname: Hopf
authors.forename: A
authors.initials: A
authors.lastname: Ries
authors.forename: R
authors.initials: R
authors.lastname: Timpl
authors.forename: E
authors.initials: E
authors.lastname: Hohenester
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry*; D007136:Immunoglobulins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013499:Surface Properties
chemical_list: D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; C029967:nidogen; C071927:perlecan