Proteopedia

Melanoma-associated antigen


Function

Melanoma-associated antigen (MAGE) are produced by tumor cells and are recognized by cytotoxic T lymphocytes[1]. Many such antigens have been identified and are classified into 2 groups with group I called cancer/testis antigens[2]. The loss of MAGE expression is observed in primary melanoma[3].

Disease

Relevance

The expression of MAGE-A1 can be a marker for the prediction of resistance to taxan-based chemotherapy in pations with gastric cancer[4]. Assessment of MAGE may provide stratification factor for active-specific immunotherapy[5].

Structural highlights

The 3D structure of the complex between MAGE-A4 and the peptide inhibitor shows the peptide to bind in a cyclic conformation. The interacting with MAGE hydrophobic pocket. MAGE residue . Additional are formed between the peptide inhibitor and MAGE[6].

3D structures of melanoma-associated antigen

Updated on 04-May-2025

MAGE; Domains: MAGE homology 101-317; PWWP 405-538

3pmi – hMAGE1 PWWP domain (mutant) – human

4v0p – hMAGEA3 MAGE homology domain
8t9a – hMAGEA3 MAGE homology domain + DDB1-DCAF12 – Cryo EM
2wa0 – hMAGEA4 MAGE homology domain
7uoa – hMAGEA4 MAGE homology domain + peptide inhibitor
6r7t – hMAGEB1 MAGE homology domain + nanobody
5hvq, 5wy5 – hMAGEG1 MAGE homology domain + NSE-1
6xr0 – hMAGEP97 + antibody


Human MAGEA4 MAGE homology domain (grey) complex with peptide inhibitor (green), ethanediol, ethylene glycol and TRIS (PDB id 7uoa)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Kirkin AF, Dzhandzhugazyan K, Zeuthen J. Melanoma-associated antigens recognized by cytotoxic T lymphocytes. APMIS. 1998 Jul;106(7):665-79. PMID:9740504 doi:10.1111/j.1699-0463.1998.tb00210.x
  2. ↑ Xiao J, Chen HS. Biological functions of melanoma-associated antigens. World J Gastroenterol. 2004 Jul 1;10(13):1849-53. PMID:15222021 doi:10.3748/wjg.v10.i13.1849
  3. ↑ Hofbauer GF, Burkhart A, Schüler G, Dummer R, Burg G, Nestle FO. High frequency of melanoma-associated antigen or HLA class I loss does not correlate with survival in primary melanoma. J Immunother. 2004 Jan-Feb;27(1):73-8. PMID:14676635 doi:10.1097/00002371-200401000-00007
  4. ↑ Suzuki T, Yoshida K, Wada Y, Hamai Y, Sentani K, Oue N, Yasui W. Melanoma-associated antigen-A1 expression predicts resistance to docetaxel and paclitaxel in advanced and recurrent gastric cancer. Oncol Rep. 2007 Aug;18(2):329-36 PMID:17611652
  5. ↑ Takeuchi H, Kuo C, Morton DL, Wang HJ, Hoon DS. Expression of differentiation melanoma-associated antigen genes is associated with favorable disease outcome in advanced-stage melanomas. Cancer Res. 2003 Jan 15;63(2):441-8 PMID:12543800
  6. ↑ Fleming MC, Chiou LF, Tumbale PP, Droby GN, Lim J, Norris-Drouin JL, Williams JG, Pearce KH, Williams RS, Vaziri C, Bowers AA. Discovery and Structural Basis of the Selectivity of Potent Cyclic Peptide Inhibitors of MAGE-A4. J Med Chem. 2022 May 26;65(10):7231-7245. doi: 10.1021/acs.jmedchem.2c00185. Epub, 2022 May 6. PMID:35522528 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c00185

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Michal Harel, Alexander Berchansky
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