Metastasis-promoting anterior gradient 2 protein has a dimeric thioredoxin fold structure and a role in cell adhesion

Pryank Patel, Christopher Clarke, Dong Liu Barraclough, Thomas Adam Jowitt, Philip Spencer Rudland, Roger Barraclough, Lu Yun Lian

    Research output: Contribution to journalArticlepeer-review

    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 Kd of 8.83 μM, 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. ©2013 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)929-943
    Number of pages14
    JournalJournal of molecular biology
    Volume425
    Issue number5
    DOIs
    Publication statusPublished - 11 Mar 2013

    Keywords

    • adhesion
    • AGR2
    • dimer
    • NMR
    • thioredoxin

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