4v0p
From Proteopedia
Crystal structure of the MAGE homology domain of human MAGE-A3
Structural highlights
FunctionMAGA3_HUMAN Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. May enhance ubiquitin ligase activity of TRIM28 and stimulate p53/TP53 ubiquitination by TRIM28. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May play a role in embryonal development and tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.[1] Publication Abstract from PubMedThe MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE-A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is predominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders. Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding.,Newman JA, Cooper CD, Roos AK, Aitkenhead H, Oppermann UC, Cho HJ, Osman R, Gileadi O PLoS One. 2016 Feb 24;11(2):e0148762. doi: 10.1371/journal.pone.0148762., eCollection 2016. PMID:26910052[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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