1. University of Zanjan, University Blvd., 45371-38791, Zanjan, I. R. Iran
Abstract
Introduction
Multiple sclerosis (ms) is a complex disease of unknown etiology. myelin basic protein is essential for the formation of functional myelin. disorder in mbp synthesis and/or autoimmunity are the major cause of ms.
angiogenesis plays a significant role in the ms lesion, perpetuating disease progression; however, its role and beings time in multiple sclerosis (ms) is unclear. thus it is assumed, treatment strategies that inhibit angiogenesis may decrease clinical and pathological signs of disease.
angiostatin, an endogenous angiogenesis inhibitor, is a fragment of plasminogen. angiostatin have significant identity with myelin basic protein (mbp), which implies the similarities in their 3-d structures. so we hypothesize autoimmunity take place against both protein and result in demyelination and angiogenesis.
Methods
The amino acid sequence of target proteins: myelin basic protein and angiostatin were retrieved from the uniprotkb/swiss-prot database. the clustalw was used for pair wise sequence alignment. the consensus secondary structural elements of the proteins were obtained through the sopm, gor iv, phd and simpa96 servers. ssea server was used for proteins secondary structure alignment.
generation of the 3d model for mbp was performed by modeller 9v20 based on the crystallographic structure of angiostatin.
Results
Protein primary sequence alignment is a way of arranging the sequences protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. however, the degree of sequence identity between mbp and angiostatin was too low to allow the angiostatin to be detected as template for modeling of mbp using basic modeling method. in another attempt, the consensus secondary structural elements of the proteins were predicted using appropriate server and aligned with ssea server. the result showed 74% identity between secondary structures of two proteins. as we know that the 3-d structure is based on the secondary structure, therefore we used 3-d structure of angiostatin (pdb id: 4dur) as tempelate for mbp modeling. the mbp model was created using modeller 9v20. the model was validated using procheck and prosa ii-web server.
Conclusion
We hypothesize the structural similarity between angiostatin and myelin basic protein cause autoimmunity take place against both protein and result in demyelination and angiogenesis.
Keywords
Angiostatin, angiogenesis, myelin basic protein and multiple sclerosis
