Computational analysis of bovine alpha-1 collagen sequences

Abstract

Bovine collagen alpha-1 is a naturally occurring extracellular matrix protein found in tendons and other connective tissues. It plays a vital role in cell growth, differentiation, attachment, and migration. Recent findings have established that collagen alpha-1 is involved in osteogenesis imperfecta phenotype in cattle but deep information about other members of this large family is not available so far. So with a view to finding a new edge and attempt to figure out a correlation among the well attributed Bovine alpha-1 collagen sequences are executed and analyzed. To do so, comparative analysis among the 28 members of collagen family has been carried out using Computational tools. Consequently, based on the physico-chemical, secondary structural, functional and phylogenetic classifications, we have selected collagen 12, 14 and 20 as targets for pathological conditions. These proteins belong to the FACIT family and significantly showed low glycine and proline content, high instability and aliphatic index. Moreover, FACIT family collagens contain multiple triple helical domains and being members of the FACIT family, bovine collagen 12, 14, 20 do not form fibrils by themselves but they are associated to collagen 1 associated fibrils. These collagen molecules might be crucial candidates to detect and understand the process of matrix remodeling in diseases especially in the arena of cellular compartments. Collagen is the most abundant family of fibrous proteins in mammals which is secreted by the connective tissue cells [1]. To note about its localization, it is found mostly in flesh and connective tissues in vertebrates [2]. Collagen structure is a triple helix with three different chains and these three alpha chains are wound around one another to form the superhelix structure which gives the long, stiff structure of collagen protein [3]. The amino acids in collagen are arranged in such a manner that glycine is present in every third residue [4]. Glycine is the smallest amino acid and thus fits perfectly in the helix and allows the alpha chains to wrap around together to form the superhelix. Collagen is rich in glycine and proline residues. So, other than glycine in every third residue, the remaining two amino acids are mostly occupied by proline. Pro-collagens are inactive precursors of collagens. During the synthesis of

collagen, pro-collagens are synthesized at first. The mature active collagen molecules are formed by the action of peptidases cleaving the pro-peptides at the N and C terminals. Vitamin C acts as a cofactor in conversion of pro-collagens to collagens. Pro-collagens are cleaved only after secretion from the cells by proteolytic enzymes. Pro-collagens are fibrillar molecules which are lot more (about a thousand fold) stable than the collagen fibrils. Cleaving of pro-collagens to collagens inside the cell can lead to catastrophic consequences. Collagen is the most abundant protein of the extracellular matrix (ECM). ECM is an intricate network of macromolecules filling the extracellular space inside the tissues. Other than collagens, ECM is rich in proteoglycans, glycoproteins and proteases [5]. In vertebrates, the main function of ECM is to serve as a scaffold to stabilize the physical structure of tissues.