Locus of a histidine-based, stable trifunctional, helix to helix collagen cross-link: stereospecific collagen structure of type I skin fibrils

Abstract

The loci of the three amino acid residues that contribute their prosthetic groups to form the stable, nonreducible, trifunctional intermolecular cross-link histidinohydroxylysinonorleucine in skin collagen fibrils were identified. Two apparently homogeneous three-chained histidinohydroxylysinonorleucine cross-linked peptides were chromatographically isolated. They were obtained from a tryptic digest of denatured unreduced 6 M guanidine hydrochloride insoluble bovine skin collagen. Amino acid and sequence analyses demonstrated that the prosthetic groups of alpha 1(I)-chain Hyl-87, alpha 1(I)-chain Lys-16c, and alpha 2(I)-chain His-92 formed the cross-link. The latter results served to define the locus of the stable, nonreducible trifunctional moiety. Identical types of analyses were performed on the three-chained peptides isolated after bacterial collagenase digestion of the cross-linked tryptic peptides. This confirmed the initial identification and location of the three peptides linked by the cross-link. In addition, data reported here provide for a correction of the micromolecular structure for the alpha 2(I) chain. Stereochemical considerations concerning this trifunctional cross-link's specific locus indicate that the steric relationships between the alpha chains of skin and skeletal tissue collagens are fundamentally different and the intermolecular relationships in skin fibrils are specific for skin. The same molecular relationships also indicate that histidinohydroxylysinonorleucine links three molecules of collagen. The stereochemistry of cross-linking for skin collagen is in accordance with and explains the X-ray findings of a 65-nm periodicity found for this tissue [Stinson, R. H., & Sweeny, P. R. (1980) Biochim. Biophys. Acta 621, 158; Brodsky, B., Eikenberry, E. F., & Cassidy, K. (1980) Biochim. Biophys. Acta 621, 162].

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma

“…Although type I collagen is also found in large quantities in soft tissues, the structure of its mature crosslinks e.g. in skin differs from that in bone (Mechanic et al, 1987). Thus it is likely that skin collagen degradation does not lead to liberation of antigens reacting in the ICTP assay.…”

Isolation and characterization of collagen from fish waste material- skin, scales and fins of Catla catla and Cirrhinus mrigala

“…Pyrrolidine rings of proline and hydroxyproline impose restrictions on the conformation of the polypeptide chain and help to strengthen the triple helix (Bae et al 2008). Hydroxylysine of 4-6 residues/1,000 residues was found in both collagens, suggesting the partial cross-linking of collagen via covalent bond (Mechanic et al 1987). Therefore, collagen from C. catla and C. mrigala might have the different molecular properties from that of other species due to the difference in imino acid content and cross-linking.…”

Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17

“…The low hydroxylation level of the telopeptides was further substantiated by the observed 5-fold elevation over normal levels for LNL, a crosslink derived from telopeptide lysyl residues. The presence of the allysine crosslinking pathway in BS bone was not accompanied by maturation to the nonreducible crosslink histidinohydroxylysinonorleucine (HHL) as in skin and cornea collagen (10)(11): only marginal amounts of HHL were detected in affected bone (Ͻ0.05 HHL͞triple helix). Pyridinium crosslink levels in bone of patient 3 showed, like patient 505 and 507, a 10-fold decrease compared with control bone (data not shown); other crosslinks were not determined.…”

“…More than ten different collagen crosslinks are known; their structure, number, and location are highly tissue specific and not related to a specific collagen type (4)(5)(6)(7)(8). Stereochemical and x-ray diffraction studies revealed that differences in molecular packing of collagen within fibrils are associated with differences in crosslink profiles (9)(10)(11)(12). Proper mineralization probably depends on a correct alignment of collagen molecules, as nucleation of calcium apatite crystals starts in the gap region, i.e., in the area adjacent to the crosslink site (9).…”