title: The 1.9-A crystal structure of the noncollagenous (NC1) domain of human placenta collagen IV shows stabilization via a novel type of covalent Met-Lys cross-link.
abstract: Triple-helical collagen IV protomers associate through their N- and C-termini forming a three-dimensional network, which provides basement membranes with an anchoring scaffold and mechanical strength. The noncollagenous (NC1) domain of the C-terminal junction between two adjacent collagen IV protomers from human placenta was crystallized and its 1.9-A structure was solved by multiple anomalous diffraction (MAD) phasing. This hexameric NC1 particle is composed of two trimeric caps, which interact through a large planar interface. Each cap is formed by two alpha 1 fragments and one alpha 2 fragment with a similar previously uncharacterized fold, segmentally arranged around an axial tunnel. Each monomer chain folds into two structurally very similar subdomains, which each contain a finger-like hairpin loop that inserts into a six-stranded beta-sheet of the neighboring subdomain of the same or the adjacent chain. Thus each trimer forms a quite regular, but nonclassical, sixfold propeller. The trimer-trimer interaction is further stabilized by a previously uncharacterized type of covalent cross-link between the side chains of a Met and a Lys residue of the alpha 1 and alpha 2 chains from opposite trimers, explaining previous findings of nonreducible cross-links in NC1. This structure provides insights into NC1-related diseases such as Goodpasture and Alport syndromes.
authors: Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82152 Martinsried, Germany. thn@biochem.mpg.de
authors: Manuel E
authors: ME
authors: Than
authors: Stefan
authors: S
authors: Henrich
authors: Robert
authors: R
authors: Huber
authors: Albert
authors: A
authors: Ries
authors: Karlheinz
authors: K
authors: Mann
authors: Klaus
authors: K
authors: Kühn
authors: Rupert
authors: R
authors: Timpl
authors: Gleb P
authors: GP
authors: Bourenkov
authors: Hans D
authors: HD
authors: Bartunik
authors: Wolfram
authors: W
authors: Bode
mesh_terms: D000595:Amino Acid Sequence; D024141:Collagen Type IV / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010920:Placenta / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D024141:Collagen Type IV; D008715:Methionine; D008239:Lysine