title: Metastasis-promoting anterior gradient 2 protein has a dimeric thioredoxin fold structure and a role in cell adhesion.
abstract: Anterior gradient 2 (AGR2) is a normal endoplasmic reticulum protein that has two important abnormal functions, amphibian limb regeneration and human cancer metastasis promotion. These normal intracellular and abnormal extracellular roles can be attributed to the multidomain structure of AGR2. The NMR structure shows that AGR2 consists of an unstructured N-terminal region followed by a thioredoxin fold. The protein exists in monomer-dimer equilibrium with a K(d) of 8.83μM, and intermolecular salt bridges involving E60 and K64 within the folded domain serve to stabilize the dimer. The unstructured region is primarily responsible for the ability of AGR2 to promote cell adhesion, while dimerization is less important for this activity. The structural data of AGR2 show a separation between potential catalytic redox activity and adhesion function within the context of metastasis and development.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Pryank
authors.initials: P
authors.lastname: Patel
authors.forename: Christopher
authors.initials: C
authors.lastname: Clarke
authors.forename: Dong Liu
authors.initials: DL
authors.lastname: Barraclough
authors.forename: Thomas Adam
authors.initials: TA
authors.lastname: Jowitt
authors.forename: Philip Spencer
authors.initials: PS
authors.lastname: Rudland
authors.forename: Roger
authors.initials: R
authors.lastname: Barraclough
authors.forename: Lu-Yun
authors.initials: LY
authors.lastname: Lian
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002850:Chromatography, Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009088:Mucoproteins; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D015513:Oncogene Proteins; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: C502296:AGR2 protein, human; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D013879:Thioredoxins