Publication

Article Metrics

Citations


Online attention

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

DOI: 10.1371/journal.pone.0148762 DOI Help

Authors: Joseph A Newman (University of Oxford) , Christopher Cooper (University of Oxford) , Annette Roos (University of Oxford) , Hazel Aitkenhead (Beatson Institute for Cancer Research) , Udo C. T. Oppermann (University of Oxford) , Hearn J. Cho (Tisch Cancer Institute, Mt Sinai School of Medicine) , Roman Osman (Department of Structural and Chemical Biology, Mount Sinai School of Medicine) , Opher Gileadi (University of Oxford) , Hiroshi Shiku
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos One , VOL 11

State: Published (Approved)
Published: February 2016
Diamond Proposal Number(s): 8421

Open Access Open Access

Abstract: The 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.

Journal Keywords: Crystal structure; Crystallization; Electron density; Molecular structure; Protein structure; Sedimentation; Sequence alignment

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: SLS