Structural model of the amino propeptide of collagen XI α1 chain with similarity to the LNS domains

Abstract

Fibrillar collagens are the principal structural molecules of connective tissues. The assembly of collagen fibrils is regulated by quantitatively minor fibrillar collagens, types V and XI. A unique amino-terminal propeptide domain of these collagens has been attributed this regulatory role. The structure of the amino terminal propeptide has yet to be determined. Low sequence similarity necessitated a secondary structure-based method to carry out homology modeling based upon the determined structure of LNS family members, named for a common structure in the laminin LG5 domain, the neurexin 1B domain and the sex hormone binding globulin. Distribution of amino acids within the model suggested glycosaminoglycan interaction and calcium binding. These activities were tested experimentally. Sequence analyses of existing genes for collagens indicate that 16 known collagen a chains may contain an LNS domain. A similar approach may prove useful for structure/function studies of similar domains in other collagens with similar domains. This will provide mechanistic details of the organization and assembly of the extracellular matrix and the underlying basis of structural integrity in connective tissues. The absolute requirement for collagen XI in skeletal growth is indicated by collagen XI deficiencies such as chondrodystrophies found in the cho/cho mouse and in humans with Stickler syndrome.

Fell–Muir Lecture: Heparan sulphate and the art of cell regulation: a polymer chain conducts the protein orchestra

“…The common Npp site is positioned in a beta‐strand in residues 147–152 and conforms to the CW XBBBXXBX motif in which the basic amino acids are exclusively lysines (Fallahi et al . ; Warner et al . ).…”

“…There is one common heparin-/HS-binding site in the NTDs of these collagens located in the so-called amino propeptide (Npp) region towards the NT, and an additional site is in an alternatively spliced region of collagen XI near to the collagenous domain (Figure 14a). The common Npp site is positioned in a beta-strand in residues 147-152 and conforms to the CW XBBBXXBX motif in which the basic amino acids are exclusively lysines (Fallahi et al 2005;Warner et al 2006). In contrast, the site in the variable region of collagen XI NTD is a long positively charged sequence containing multiple clusters of arg/lys residues (Warner et al 2006) somewhat analogous to the unique HS-binding region in SDF1-gamma.…”

The Structure of Glycosaminoglycans and their Interactions with Proteins

“…Simulated annealing and genetic algorithms have been extensively used to dock GAGs to their putative proteins or receptors (137,144,(154)(155)(156)(157)(158). It is clear that the prediction of binding energies of heparin and related sulphated GAGs to their biological targets requires a large number of docking evaluations in order to achieve energy convergence and sufficient conformational sampling.…”

Differential Expression of Collagen Type V and XI α-1 in Human Ascending Thoracic Aortic Aneurysms

“…This differential regulation has been previously demonstrated in smooth muscle cells in the tunica media of ATAAs [19, 20] and in aortic smooth muscle cells in culture [17], and has been suggested as a possible mechanism modulating ECM remodeling. Recent studies have shown that the amino-terminal propeptide of collagen α1(XI) contains a well-characterized heparin binding domain [21, 22]. This heparin binding domain has been shown to interact with specific integrin receptors that promote the regulation of expression and activity of matrix metalloproteinases (MMPs) [23].…”