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PDBsum entry 5hvq
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References listed in PDB file
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Key reference
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Title
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Structures of two melanoma-Associated antigens suggest allosteric regulation of effector binding.
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Authors
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J.A.Newman,
C.D.Cooper,
A.K.Roos,
H.Aitkenhead,
U.C.Oppermann,
H.J.Cho,
R.Osman,
O.Gileadi.
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Ref.
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Plos One, 2016,
11,
e0148762.
[DOI no: ]
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PubMed id
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Abstract
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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.
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