The role of the main noncollagenous domain (NC1) in type IV collagen self-assembly.

Tsilibary, Effie C.; Charonis, Aristidis S.

doi:10.1083/jcb.103.6.2467

Cited by 86 publications

(50 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Emerging evidence suggests that the C-terminal propeptide of the procollagen molecules plays a key role in the chain-specific recognition (3)(4)(5)(6)(7)(8). Bulleid and colleagues (9) demonstrated that transferring the C-propeptide of pro-␣1(III) chain to the corresponding region of the naturally heterotrimeric pro-␣2(I) molecule was sufficient to direct the new hybrid molecules to form stable homotrimers.…”

mentioning

confidence: 99%

Mechanism of Chain Selection in the Assembly of Collagen IV

Khoshnoodi

Sigmundsson

Cartailler

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Collagens comprise a large superfamily of extracellular matrix proteins that play diverse roles in tissue function. The mechanism by which newly synthesized collagen chains recognize each other and assemble into specific triple-helical molecules is a fundamental question that remains unanswered. Emerging evidence suggests a role for the non-collagenous domain (NC1) located at the C-terminal end of each chain. In this study, we have investigated the molecular mechanism underlying chain selection in the assembly of collagen IV. Using surface plasmon resonance, we have determined the kinetics of interaction and assembly of the ␣1(IV) and ␣2(IV) NC1 domains. We show that the differential affinity of ␣2(IV) NC1 domain for dimer formation underlies the driving force in the mechanism of chain discrimination. Given its characteristic domain recognition and affinity for the ␣1(IV) NC1 domain, we conclude that the ␣2(IV) chain plays a regulatory role in directing chain composition in the assembly of (␣1) 2 ␣2 triple-helical molecule. Detailed crystal structure analysis of the [(␣1) 2 ␣2] 2 NC1 hexamer and sequence alignments of the NC1 domains of all six ␣-chains from mammalian species revealed the residues involved in the molecular recognition of NC1 domains. We further identified a hypervariable region of 15 residues and a ␤-hairpin structural motif of 13 residues as two prominent regions that mediate chain selection in the assembly of collagen IV. To our knowledge, this report is the first to combine kinetics and structural data to describe molecular basis for chain selection in the assembly of a collagen molecule.Collagens comprise a major superfamily of extracellular matrix (ECM) 3 proteins that play a key role in the structural integrity of all tissues. At least 27 different collagen types, consisting of 42 distinct gene products, have been identified in vertebrates, underlining their vast diversity in biological functions such as tissue compartmentalization and specialization during the development (1). In the endoplasmic reticulum, the newly synthesized collagen chains assemble into triple-helical molecules with specific chain compositions, which oligomerize to form supramolecular structures, including filaments and networks after secretion to the ECM.Some collagens are obligate homotrimers, such as collagen III, which comprises three identical pro-␣1(III) chains forming an ␣1(III) 3 procollagen, whereas others form heterotrimers containing at least one different ␣-chain; such as collagen I (2). Despite significant sequence identity and a propensity to form triple helices, procollagen chains have an extraordinary ability to discriminate between each other in the endoplasmic reticulum to form specific collagen types. For example, skin fibroblasts express six highly homologous but genetically distinct fibrilforming procollagen chains that are assembled in a type-specific manner to form type I, III, and V collagens. The mechanism by which different collagen chains are selected for assembly is a fundamental question...

show abstract

mentioning

confidence: 99%

Mechanism of Chain Selection in the Assembly of Collagen IV

Khoshnoodi

Sigmundsson

Cartailler

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…For the NC1 domain we were able to indicate the presence of cross-linking by showing trimers (highmolecular weight material at 90 kD) and tetrameres (high-molecular weight material at 110 kD). These aggregates cannot found be in native tissue [30,44].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and biophysical alterations of the 7S and NC1 domain of collagen IV from human diabetic kidneys

et al. 1998

View full text Add to dashboard Cite

Glycation and glycoxidative reactions have been recognised to be a major pathogenetic principle for biochemical and biophysical alterations of proteins in diabetes mellitus [1±3]. Both processes have been shown to increase in humans with age and even more in patients with diabetes mellitus with the duration of the disease [4±8].Glycoxidative reactions, e. g. the Maillard reaction, are initiated by the condensation of a reducing sugar with an e-amino group of lysyl-or hydroxylysyl-residues of proteins [9]. The resulting Schiff-base is stabilised subsequently by Amadori rearrangement and processed further in very diverse and not yet fully elucidated chemical reactions resulting in a variety of cross-linked compounds. Only a small number of those, including pentosidine, have been characterised in structure and chemical composition [2, 10±16]. Glycation of proteins is associated with the formation of high-molecular aggregates that are stabilised by non-reducible cross-linking components [13, 17±18] with characteristic fluorescence spectra [6,19,20]. Circular dichroism (CD) spectroscopy studies of glycated proteins exhibited a damaging effect of the modifications on protein structure and stability [21,22].In diabetic nephropathy the disordered morphology and functional deficiency of the glomerular basement membrane (GBM) has been explained by glycation of the collagen IV network providing the mechanical scaffold of the membrane texture. Collagen IV monomers consist of a collagenous major triplehelical domain with two specific cross-linking domains, the NC1 domain at the C-terminal end and the N-terminus the 7S domain [23±26], facilitating Diabetologia (1998) Summary Glycation of basement membrane collagen IV has been implicated as a major pathogenetic process leading to diabetic microvascular complications. To evaluate the relevance of carbohydrate-induced modifications on collagen IV in diabetic nephropathy, we isolated the cross-linking domains 7S and NC1 from the glomerular basement membrane (GBM) of patients with diabetes mellitus. Modifications characteristic for glycated proteins were identified when the domains from diabetic kidney were compared with the same domains from human placenta as an unmodified control. In both domains a marked formation of inter-and intramolecular cross links could be demonstrated by SDS-PAGE. Furthermore circular dichroism studies showed a decrease in helicity of the 7S domain from human diabetic kidneys of 13 %, indicating denaturation already at room temperature. Thermal transition profiles, showing a shift of the denaturation temperature towards a lower temperature, with loss of a distinct second melting point, confirmed this observation. Our data provide further evidence for a possible role of protein-modification by glycoxidative reactions in the onset of diabetic nephropathy in vivo. [Diabetologia (1998

show abstract

“…Preparation of Anti-NC1 Antibodies and Their Fab FragmentsAnti-NC1 antibodies were produced as described previously (29). Briefly, isolated NC1 in complete Freund's adjuvant was injected subcutaneously in female New Zealand rabbits three times at two-week intervals.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were cultured in Dulbecco's minimal essential medium (DMEM) supplemented with 20% fetal calf serum (Sigma), 15 mM HEPES, 25 mM glucose, and antibiotics amphotericin (0.25 g/ml), penicillin G (100 IU/ml), and streptomycin (100 g/ml). Cells were used through passage 5-9, grown in T-75 flasks till 75-80% confluence, and then metabolically labeled for 18 h with 0.5 mCi of Isolation and Purification of Type IV Collagen and Type IV Collagen Domains-COL-IV was isolated from (EHS) as described previously (29). The major triple helix-rich domain, which lacks the NC1 and 7 S domains, was obtained by a light digestion of EHS-derived COL-IV with pepsin (Cooper Biomedical Inc.) as described by Yurchenco and Furthmayr (30).…”

Section: Methodsmentioning

confidence: 99%

“…This fragment also lacks some pepsin-sensitive interruptions in the triple helical domain, including the sequence contained in peptide Hep-III (31). The major non-collagenous domain or NC1 of COL-IV was obtained by digestion of EHS-derived COL-IV with collagenase (CLSPA Cooper Biomedical Inc.) as described previously (29,32). Peptide HEP-III was synthesized by the method of Barany and Merrifield (33) on a solid-phase support as described previously (5).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation