4qmg
From Proteopedia
The Structure of MTDH-SND1 Complex Reveals Novel Cancer-Promoting Interactions
Structural highlights
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 PubMedMetadherin (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
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Categories: Human | Large Structures | Guo, F | Kang, Y | Satyshur, K | Stanevich, V | Wan, L | Xing, Y | Breast cancer | Dna/rna-binding | Mirna-mediated silencing | Mtdh | Nuclease | Sn domain | Snd1 | Transcription | Tumorigenesis
