Structural highlights
Function
NSE3_HUMAN Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest.[1]
Publication Abstract from PubMed
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.
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.
See Also
References
- ↑ Doyle JM, Gao J, Wang J, Yang M, Potts PR. MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell. 2010 Sep 24;39(6):963-74. PMID:20864041 doi:10.1016/j.molcel.2010.08.029
- ↑ Newman JA, Cooper CD, Roos AK, Aitkenhead H, Oppermann UC, Cho HJ, Osman R, Gileadi O. Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding. PLoS One. 2016 Feb 24;11(2):e0148762. doi: 10.1371/journal.pone.0148762., eCollection 2016. PMID:26910052 doi:http://dx.doi.org/10.1371/journal.pone.0148762
