Prediction of domain organisation and secondary structure of thyroid peroxidase, a human autoantigen involved in destructive thyroiditis

TY - JOUR

T1 - Prediction of domain organisation and secondary structure of thyroid peroxidase, a human autoantigen involved in destructive thyroiditis

AU - Banga, J. Paul

AU - Mahadevan, Daruka

AU - Barton, Geoffrey J.

AU - Sutton, Brian J.

AU - Saldanha, Jose W.

AU - Odell, Eddy

AU - McGregor, Alan M.

PY - 1990/6/18

Y1 - 1990/6/18

N2 - Organ specific autoimmune diseases are relatively common immunological disorders in man which include thyroid autoimmune disease, insulin-dependent diabetes mellitus and myasthenia gravis. The target autoantigens in some of these diseases have recently been characterised. In thyroid autoimmune disease this includes the key enzyme, thyroid peroxidase (TPO), which is involved in the generation of thyroid hormone. Structural knowledge about autoantigens such as thyroid peroxidase will allow a greater understanding of the interaction between autoantigens and the aberrant immune response, and facilitate the development of strategies for antigen-specific therapeutic manipulation. We report here a prediction of the secondary structure of thyroid peroxidase, together with the results of circular dichroic spectroscopy of a homologous purified enzyme. A combination of 3 secondary structure prediction programs has been used, following multiple sequence alignment, and TPO has been found to consist mainly of alpha-helical conformation, with little beta-sheet present. This structure prediction, together with knowledge of the exon-intron boundaries allows a model for the domain organisation of the TPO molecule to be proposed.

AB - Organ specific autoimmune diseases are relatively common immunological disorders in man which include thyroid autoimmune disease, insulin-dependent diabetes mellitus and myasthenia gravis. The target autoantigens in some of these diseases have recently been characterised. In thyroid autoimmune disease this includes the key enzyme, thyroid peroxidase (TPO), which is involved in the generation of thyroid hormone. Structural knowledge about autoantigens such as thyroid peroxidase will allow a greater understanding of the interaction between autoantigens and the aberrant immune response, and facilitate the development of strategies for antigen-specific therapeutic manipulation. We report here a prediction of the secondary structure of thyroid peroxidase, together with the results of circular dichroic spectroscopy of a homologous purified enzyme. A combination of 3 secondary structure prediction programs has been used, following multiple sequence alignment, and TPO has been found to consist mainly of alpha-helical conformation, with little beta-sheet present. This structure prediction, together with knowledge of the exon-intron boundaries allows a model for the domain organisation of the TPO molecule to be proposed.

KW - Amino acid sequence

KW - Animals

KW - Autoantigens

KW - Circular dichroism

KW - Complement C4b

KW - Electron transport complex IV

KW - Epidermal growth factor

KW - Humans

KW - Hydrogen bonding

KW - Iodide peroxidase

KW - Molecular sequence data

KW - Peroxidase

KW - Protein conformation

KW - Swine

KW - Thyroid gland

U2 - 10.1016/0014-5793(90)81524-R

DO - 10.1016/0014-5793(90)81524-R

M3 - Article

C2 - 2163885

SN - 0014-5793

VL - 266

SP - 133

EP - 141

JO - FEBS Letters

JF - FEBS Letters

IS - 1-2

ER -