Thyroglobulin structure and function: recent advances.
Thyroglobulin is a large-size iodoglycoprotein specific to thyroid tissue and is the substrate for the synthesis of thyroid hormones, thyroxine and 3,5,3'-triiodothyronine. Recent studies, which greatly benefited from recombinant DNA methodologies, improved the knowledge of several structural features of this dimeric protein and permitted insights into some structure-function relationships. Analysis-function of the primary structure of the human thyroglobulin monomer revealed several main characteristics: 1) 3 types of internal homologies; 2) extensive homology with the bovine thyroglobulin monomer and known partial sequences in the thyroglobulins of other mammalian species; 3) significant homologies with 2 other non-thyroid proteins (acetylcholinesterase and the invariant chain of the Ia class II histocompatibility antigen); 4) a terminal localization of the hormonogenic sites at both ends of the monomer. Current studies aim at determining conformational characteristics, understanding the molecular mechanisms of thyroid hormone formation and unraveling those interactions which in the thyroid cell and the thyroid follicle will permit this large pro-hormone to synthesize and release a few small thyroid hormone molecules. A more precise knowledge of this molecule in higher vertebrates and during evolution would impart valuable information concerning thyroid pathology, since thyroglobulin has been implicated in some genetic and in autoimmune thyroid diseases.
Malthièry
Y
Y
Laboratoire de Biochimie Médicale, INSERM U38, CNRS UA178, Faculté de Médecine, Marseille, France.
Marriq
C
C
Bergé-Lefranc
J L
JL
Franc
J L
JL
Henry
M
M
Lejeune
P J
PJ
Ruf
J
J
Lissitzky
S
S
D000595:Amino Acid Sequence; D004247:DNA / Q000302:isolation & purification; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012333:RNA, Messenger / Q000302:isolation & purification; D013954:Thyroglobulin / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D004247:DNA; D013954:Thyroglobulin