Minor fibrillar collagens, variable regions alternative splicing, intrinsic disorder, and tyrosine sulfation

Abstract

Minor fibrillar collagen types V and XI, are those less abundant than the fibrillar collagens types I, II and III. The alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable region. Genomic variation and, in some cases, extensive alternative splicing contribute to the unique sequence characteristics of the variable region. While unique expression patterns in tissues exist, the functions and biological relevance of the variable regions have not been elucidated. In this review, we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha chains. Analysis of biochemical similarities among the peptides encoded by each exon of the variable region suggest the potential for shared function. The alternative splicing, conservation of biochemical characteristics in light of low sequence conservation, and evidence for intrinsic disorder, suggests modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.

Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations from South Africa and Australia

“…COL5A1 encodes the α1 chain of type V collagen, which plays an important role in collagen fibril assembly, the basic building block of tendons 8. Type XI collagen, which is encoded by the COL11A1 , COL11A2 and COL2A1 genes,10 shares structural and functional homology with type V collagen 11…”

“…Type XI collagen, a heterotrimer consisting of α1(XI), α2(XI) and α3(XI) chains encoded by the COL11A1 (chromosome 1p21), COL11A2 (chromosome 6p21.3) and COL2A1 (chromosome 12q13.11) genes, respectively,10 shares structural and functional homology with type V collagen 11. Although predominately expressed in cartilage,11 type XI collagen is also expressed in developing tendons 12…”

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis

“…Collagens type I, II, III, V, XI, XXIV, and XXVII are described as the fibrillar collagens due to their formation of collagen fibrils in the ECM [3,4,5,6]. Of these, the fibrillar collagens are further classified by their relative abundance in fibrils—types I, II, and III are referred to as the major fibrillar collagens, while types V and XI are quantitatively minor [6,7].…”

“…Of these, the fibrillar collagens are further classified by their relative abundance in fibrils—types I, II, and III are referred to as the major fibrillar collagens, while types V and XI are quantitatively minor [6,7]. Sequence analysis predicts that types XXIV and XXVII form a third clade of fibrillar collagen genes [3,4,8].…”

Role of tyrosine-sulfated proteins in retinal structure and function

“…Procollagen V and Procollagen III have been shown to be tyrosine-sulfated (Fessler et al 1986; Jukkola et al 1986). Sulfinator analysis predicts that three human minor fibrillar collagens, Col5a1, Col11a1, and Col11a2, are tyrosine-sulfated (Fang et al 2012). Since collagens bind to other proteins in the ECM, such as fibronectin (Chandrasekhar et al 1983; Dzamba et al 1993), integrins such as α1β1 and α2β1 (Nykvist et al 2000), morphogenetic protein-2 (BMP-2; Morin et al 2006), and hepatocyte growth factor (HGF; Schuppan et al 1998), tyrosine sulfation on collagens may be involved in optimum binding to these ECM proteins.…”