| Structural highlights
4qmg is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | |
| Related: | 3omc, 2e6n, 3omg, 3bdl, 2hqe, 2hqx |
| Gene: | Metadherin (MTDH) and Staphylococcal nuclease domain containing 1 (SND1), SND1, TDRD11 (HUMAN), AEG1, LYRIC, Metadherin (MTDH), MTDH (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SND1_HUMAN] Functions as a bridging factor between STAT6 and the basal transcription factor. Plays a role in PIM1 regulation of MYB activity. Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2).[1] [LYRIC_HUMAN] Downregulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance.[2] [3] [4] [5]
Publication Abstract from PubMed
Metadherin (MTDH) and Staphylococcal nuclease domain containing 1 (SND1) are overexpressed and interact in diverse cancer types. The structural mechanism of their interaction remains unclear. Here, we determined the high-resolution crystal structure of MTDH-SND1 complex, which reveals an 11-residue MTDH peptide motif occupying an extended protein groove between two SN domains (SN1/2), with two MTDH tryptophan residues nestled into two well-defined pockets in SND1. At the opposite side of the MTDH-SND1 binding interface, SND1 possesses long protruding arms and deep surface valleys that are prone to binding with other partners. Despite the simple binding mode, interactions at both tryptophan-binding pockets are important for MTDH and SND1's roles in breast cancer and for SND1 stability under stress. Our study reveals a unique mode of interaction with SN domains that dictates cancer-promoting activity and provides a structural basis for mechanistic understanding of MTDH-SND1-mediated signaling and for exploring therapeutic targeting of this complex.
Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex.,Guo F, Wan L, Zheng A, Stanevich V, Wei Y, Satyshur KA, Shen M, Lee W, Kang Y, Xing Y Cell Rep. 2014 Sep 25;8(6):1704-13. doi: 10.1016/j.celrep.2014.08.033. Epub 2014 , Sep 18. PMID:25242325[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tong X, Drapkin R, Yalamanchili R, Mosialos G, Kieff E. The Epstein-Barr virus nuclear protein 2 acidic domain forms a complex with a novel cellular coactivator that can interact with TFIIE. Mol Cell Biol. 1995 Sep;15(9):4735-44. PMID:7651391
- ↑ Kang DC, Su ZZ, Sarkar D, Emdad L, Volsky DJ, Fisher PB. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 2005 Jun 20;353(1):8-15. PMID:15927426 doi:http://dx.doi.org/S0378-1119(05)00194-0
- ↑ Emdad L, Sarkar D, Su ZZ, Randolph A, Boukerche H, Valerie K, Fisher PB. Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Cancer Res. 2006 Feb 1;66(3):1509-16. PMID:16452207 doi:http://dx.doi.org/66/3/1509
- ↑ Sarkar D, Park ES, Emdad L, Lee SG, Su ZZ, Fisher PB. Molecular basis of nuclear factor-kappaB activation by astrocyte elevated gene-1. Cancer Res. 2008 Mar 1;68(5):1478-84. doi: 10.1158/0008-5472.CAN-07-6164. PMID:18316612 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-6164
- ↑ Hu G, Chong RA, Yang Q, Wei Y, Blanco MA, Li F, Reiss M, Au JL, Haffty BG, Kang Y. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell. 2009 Jan 6;15(1):9-20. PMID:19111877 doi:http://dx.doi.org/S1535-6108(08)00379-6
- ↑ Guo F, Wan L, Zheng A, Stanevich V, Wei Y, Satyshur KA, Shen M, Lee W, Kang Y, Xing Y. Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex. Cell Rep. 2014 Sep 25;8(6):1704-13. doi: 10.1016/j.celrep.2014.08.033. Epub 2014 , Sep 18. PMID:25242325 doi:http://dx.doi.org/10.1016/j.celrep.2014.08.033
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