Myelin Basic Protein: Location of Multiple Independent Antigenic Regions

Driscoll, Bernard F.; Kramer, A. J.; Kies, Marian W.

doi:10.1126/science.184.4132.73

Cited by 57 publications

(12 citation statements)

References 14 publications

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“…Breakdown of a membranebound component such as basic protein to form multiple encephalitogenic products has many intriguing possibilities. Some but not all of the breakdown products can react with antibody to basic protein [34]. Solubilization by breakdown of membrane proteins may precede interaction at the relevant immunological sites.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Instability of Myelin Proteins

Benuck¹,

Marks²,

Hashim

1975

European Journal of Biochemistry

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Myelin basic protein, purified from bovine spinal cord, is cleaved by a purified bovine brain acid proteinase to yield three peptide fragments which were purified by gel filtration procedures combined with preparative gel electrophoresis. The purity of the fragments was established by end group analysis, amino acid analysis, polyacrylamide disc gel electrophoresis, and by their encephalitogenic activity. Chemical and biological characterization shows that one'peptide, (peptide 11), originates from the N-terminal end of the basic protein and contains residues 1-43; a second peptide, (peptide I), contains residues 44-89 and a third peptide (peptide III), originates from the C-terminal region with an N-terminal phenylalanine, residue 90, through arginine, residue 170, of the basic protein. The combined amino acid composition of the three fragments account for the amino acid content of the basic protein. The structure of the three peptides demonstrates that the purified brain acid proteinase selectively cleaves the two phenylalanine-phenylalanine linkages formed between residues 43-44 and 89-90 of the basic protein molecule. This study shows that cathepsin D could be the endogenous enzyme responsible for the breakdown of basic protein to form smaller encephalitogenic fragments, some of which are known to be present in crude tissue extracts.It was established in previous studies that most myelin protein components are subject to turnover [l]. Basic protein of myelin is of particular interest because it is known to induce an autoimmune disease associated with demyelination, experimental allergic encephalomyelitis. Previously, Einstein et af. [2] showed that basic protein can be cleaved by acid proteinase to form smaller encephalitogenic fragments, but the composition of these, and the nature of the susceptible bonds cleaved, have never been established. Indeed, early studies on the isolation and structure of basic protein were accompanied by autolysis during extraction, leading to the fortuitous isolation of polypeptide fragments, some of which were encephalitogenic in a particular species [3-51. Therefore, it is of some interest to establish the exact mechanism of basic protein breakdown using a known intracellular enzyme, since this may have some bearing on demyelinating processes in experimental disease and, in addition, provide some insight into the general mechanism of protein turnover in brain. A limited and specific degradation of basic protein could lead to the production of smaller (diffusible) peptides capable of interaction at the immunological sites related to autoimmune phenomena. The present work was designed to determine the nature of the peptide bonds split by the action of brain cathepsin D, as well as the structure and biological activity of the resultant peptides based on the known structure of bovine basic protein [6]. In other tissues, Coffey and de Duve [7] showed that catheptic activity of lysosomes appear to play a rate-limiting role in the pathways of protein breakdown. Thus, studies on the...

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Section: Discussionmentioning

confidence: 99%

Metabolic Instability of Myelin Proteins

Benuck¹,

Marks²,

Hashim

1975

European Journal of Biochemistry

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“…Adsorption of anti-BP antisera with matching disc gel cutouts permitted the detection of peptides which might not have precipitated but which could bind anti-BP antibodies and thus interfere with the ability of whole BP or of known B P peptides [3, 19,21,24,251 to precipitate in similar immunodiffusion experiments.…”

Section: Csf Was Obtained From Patients With a Variety Of Diseasesmentioning

confidence: 99%

Degradation of myelin basic protein by cerebrospinal fluid: Preservation of antigenic determinants under physiological conditions

Alvord

Hruby

Sires

1979

Annals of Neurology

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Cerebrospinal fluid contains several proteolytic enzymes that can degrade myelin basic protein (BP) under physiological conditions into peptide fragments of various sizes which still contain antigenic determinants capable of binding antibodies to BP. These enzymes are optimally active in either acid (pH 4) or nuetral (pH 7 to 8) conditions and can be characterized by the nature of the BP peptide fragments produced. Proteinases resembling cathepsin D, thrombin, plasmin (fibrinolysin), or kallikrein are present in variable amounts in CSF. No relationship to any particular disease has yet been established.

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“…In guinea pigs, at least three independent sites that are antigenic determinants for antibody have been determined in the basic protein (Driscoll et al, 1974b). These include the regions between residues 43 and 88,88 and 115, and 116 and 169.…”

Section: Antibody Response To Basic Proteinmentioning

confidence: 99%

Myelin

1984

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Myelin Basic Protein: Location of Multiple Independent Antigenic Regions

Cited by 57 publications

References 14 publications

Metabolic Instability of Myelin Proteins

Metabolic Instability of Myelin Proteins

Degradation of myelin basic protein by cerebrospinal fluid: Preservation of antigenic determinants under physiological conditions

Myelin

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