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

Proc Natl Acad Sci U S A. 2002 May 14;99(10):6607-12. doi: 10.1073/pnas.062183499.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Collagen Type IV / chemistry*
  • Collagen Type IV / genetics
  • Crystallography, X-Ray
  • Female
  • Humans
  • Lysine / chemistry
  • Methionine / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Placenta / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid


  • Collagen Type IV
  • Methionine
  • Lysine

Associated data

  • PDB/1LI1