Revisiting iodination sites in thyroglobulin with an organ-oriented shotgun strategy. 2011

Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
Commissariat à l'Energie Atomique, DSV, iBEB, Laboratoire des Transporters en Imagerie et Radiothérapie en Oncologie, Bagnols-sur-Cèze F-30207, France. alain.dedieu@cea.fr

Thyroglobulin (Tg) is secreted by thyroid epithelial cells. It is essential for thyroid hormonogenesis and iodine storage. Although studied for many years, only indirect and partial surveys of its post-translational modifications were reported. Here, we present a direct proteomic approach, used to study the degree of iodination of mouse Tg without any preliminary purification. A comprehensive coverage of Tg was obtained using a combination of different proteases, MS/MS fragmentation procedures with inclusion lists and a hybrid mass high-resolution LTQ-Orbitrap XL mass spectrometer. Although only 16 iodinated sites are currently known for human Tg, we uncovered 37 iodinated tyrosine residues, most of them being mono- or diiodinated. We report the specific isotopic pattern of thyroxine modification, not recognized as a normal peptide pattern. Four hormonogenic sites were detected. Two donor sites were identified through the detection of a pyruvic acid residue in place of the initial tyrosine. Evidence for polypeptide cleavages sites due to the action of cathepsins and dipeptidyl proteases in the thyroid were also detected. This work shows that semi-quantitation of Tg iodination states is feasible for human biopsies and should be of significant medical interest for further characterization of human thyroid pathologies.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011499 Protein Processing, Post-Translational Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility. Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002403 Cathepsins A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES. Cathepsin
D006728 Hormones Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013954 Thyroglobulin
D013961 Thyroid Gland A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively. Thyroid,Gland, Thyroid,Glands, Thyroid,Thyroid Glands,Thyroids
D014020 Tissue Extracts Preparations made from animal tissues or organs (ANIMAL STRUCTURES). They usually contain many components, any one of which may be pharmacologically or physiologically active. Tissue extracts may contain specific, but uncharacterized factors or proteins with specific actions. Extracts, Tissue

Related Publications

Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
October 1996, Archives of biochemistry and biophysics,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
January 1966, Bulletin de la Societe de chimie biologique,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
January 1967, Acta biologica et medica Germanica,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
March 1984, Endocrinology,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
November 1981, Molecular and cellular endocrinology,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
August 1967, Folia endocrinologica,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
April 1975, Molecular and cellular endocrinology,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
March 1966, The Journal of biological chemistry,
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
January 2011, Hormones (Athens, Greece),
Alain Dedieu, and Jean-Charles Gaillard, and Thierry Pourcher, and Elisabeth Darrouzet, and Jean Armengaud
December 1980, Acta endocrinologica,
Copied contents to your clipboard!