Comparative analysis of the noncollagenous NC1 domain of type IV collagen: Identification of structural features important for assembly, function, and pathogenesis (original) (raw)

The NC1 Domain of Collagen IV Encodes a Novel Network Composed of the alpha 1, alpha 2, alpha 5, and alpha 6 Chains in Smooth Muscle Basement Membranes

Journal of Biological Chemistry, 2001

Type IV collagen, the major component of basement membranes (BMs), is a family of six homologous chains (␣1-␣6) that have a tissue-specific distribution. The chains assemble into supramolecular networks that differ in the chain composition. In this study, a novel network was identified and characterized in the smooth muscle BMs of aorta and bladder. The noncollagenous (NC1) hexamers solubilized by collagenase digestion were fractionated by affinity chromatography using monoclonal antibodies against the ␣5 and ␣6 NC1 domains and then characterized by two-dimensional gel electrophoresis and Western blotting. Both BMs were found to contain a novel ␣1⅐␣2⅐␣5⅐␣6 network besides the classical ␣1⅐␣2 network. The ␣1⅐␣2⅐␣5⅐␣6 network represents a new arrangement in which a protomer (triplehelical isoform) containing the ␣5 and ␣6 chains is linked through NC1-NC1 interactions to an adjoining protomer composed of the ␣1 and ␣2 chains. Re-association studies revealed that the NC1 domains contain recognition sequences sufficient to encode the assembly of both networks. These findings, together with previous ones, indicate that the six chains of type IV collagen are distributed in three major networks (␣1⅐␣2, ␣3⅐␣4⅐␣5, and ␣1⅐␣2⅐␣5⅐␣6) whose chain composition is encoded by the NC1 domains. The existence of the ␣1⅐␣2⅐␣5⅐␣6 network provides a molecular explanation for the concomitant loss of ␣5 and ␣6 chains from the BMs of patients with X-linked Alport's syndrome.

Nucleotide sequence coding for the human type IV collagen α2 chain cDNA reveals extensive homology with the NC1 domain of α1 (IV) but not with the collagenous domain or 3untranslated region

Febs Letters, 1987

We have isolated two overlapping cDNA clones that provide the complete nucleotide sequence coding for the NC-l domain and 3'-untranslated region of the cl, chain of human type IV collagen as well as a sequence encoding 232 residues of the collagenous domain. An extensive homology was observed between the sequences of the NC-l domain of the q(IV) and %(IV) chains, but considerably less between the sequences encoding collagenous and 3'-untranslated regions. There were four interruptions in the collagenous sequence studied whereas the comparable region of the aI chain had only two. A potential oligosaccharide attachment site was found in a 6-residue long interruption of the collagenous domain but none in the NC-l domain. Basement membrane; Collagen; Sequence homology; (Human) Published by Elsevier Science Publishers B. V. (Biomedical Division) 00145793/87/$3.50 0 1987 Federation of European Biochemical Societies 281 Volume 216, number 2

The Complete Primary Structure for the α1-Chain of Mouse Collagen IV

Journal of Biological Chemistry, 1989

We report here the complete nucleotide and amino acid sequences for the al-chain of mouse collagen IV which is 1669 amino acids in length, including a putative 27-residue signal peptide. In comparison with the amino acid sequence for the a2-chain (Saus, J.,

Extensive homology between the carboxyl-terminal peptides of mouse α1(IV) and α2(IV) collagen

Journal of Biological Chemistry

We have determined the complete primary structure for the carboxyl-terminal peptides of mouse al(1V) and a2(IV) collagen, which have 229 and 227 amino acids, respectively. The amino acid sequences are 63% identical and conservatively substituted in 28 positions. A striking feature of these peptides is that the first half of each sequence is homologous with the second half, 37% in cul(1V) and 36% in a2(IV). These results suggest that the carboxyl-terminal peptides of type IV collagen are closely related in their structure and evolution. Presumably, they were first derived by internal duplication of a common ancestral DNA sequence which later, by gene duplication, gave rise to the two different but homologous carboxyl-terminal peptides of type IV collagen.

Identification of binding partners interacting with the α1-N-propeptide of type V collagen

Biochemical Journal, 2011

The predominant form of type V collagen is the [α1(V)] 2 α2(V) heterotrimer. Mutations in COL5A1 or COL5A2, encoding respectively the α1(V)-and α2(V)-collagen chain, cause classic Ehlers-Danlos syndrome (EDS), a heritable connective tissue disorder, characterized by fragile hyperextensible skin and joint hypermobility. Approximately half of the classic EDS cases remains unexplained. Type V collagen controls collagen fibrillogenesis through its conserved α1(V)-amino(N)propeptide domain. To gain insight into the role of this domain, a yeast-two-hybrid screen among proteins expressed in human dermal fibroblasts was performed utilizing the amino(N)-propeptide as a bait. We identified 12 interacting proteins including extracellular matrix proteins and proteins involved in collagen biosynthesis. Eleven interactions were confirmed by surface plasmon resonance and/or coimmunoprecipitation: α1(I)-and α2(I)-collagen chains, α1(VI)-, α2(VI)-and α3(VI)-collagen chains, tenascin-C, fibronectin, procollagen C-proteinase enhancer-1 (PCPE-1), tissue inhibitor of metalloproteinases-1, matrix metalloproteinase-2 and transforming growth factor-β1.