Investigating the mutations and structure of short part of collagen type I in osteogenesis imperfecta type III

Abstract

The extracellular matrix for connective tissues displays an abstruse alloy of changeable members of various protein families describing structural validity and different physiological functions. The most important component of extracellular matrix is collagen. Collagens’ large family in humans is consisting of at least 27 members (described as being type I to XXVII) with 42 distinguished polypeptide chains. Collagen type I is the most plentiful and extensively expressed collagen in human which is comprising of 2 a1 chains and one a2 chain and their gens are located at the different loci,COL1A1 and COL1A2 respectively. Mutation at these loci causes various connective tissue disorders such as Osteogenesis Imperfecta(OI). Osteogenesis Imperfecta (OI) or Vrolik's syndrome is a heterogeneous group of inherited conditions which has different types but, Type III is individualized among the other classifications because this type is the "Progressive Deforming" type. This study reports a comparative investigation on a short sequence of a1 and a2 chains near the c-terminal positions by the means of mutated and normal cases. Our focus in this study was on two point mutations near the end of each chain which in a1 are Gly973Ser & Gly1009Ser and in a2 are Gly997Asn & Gly1006Ala by extracting our desired parts of a1&a2 sequences from UniProt and modeling them by using EsyPred3D with applying the most identical pdb file obtained from rcsb & BLAST as template. After visualization and doing mutation by PyMOL, the differences in their sequence have been investigated by Jalview. Our obtained results from simulation of normal and mutated structures of a1&a2 by GROMACS software demonstrated that substitution of Gly by Ser in a1 and by Ala in a2 affected on the function of protein, on the other hand, substitution of Gly by Asn in a2 effected on the structure of protein.