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Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex

Author(s): Guo, Feng; Wan, Liling; Zheng, Aiping; Stanevich, Vitali; Wei, Yong; et al

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Abstract: 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.
Publication Date: 18-Sep-2014
Citation: Guo, Feng, Wan, Liling, Zheng, Aiping, Stanevich, Vitali, Wei, Yong, Satyshur, Kenneth A, Shen, Minhong, Lee, Woojong, Kang, Yibin, Xing, Yongna. (2014). Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex. Cell Reports, 8 (6), 1704 - 1713. doi:10.1016/j.celrep.2014.08.033
DOI: doi:10.1016/j.celrep.2014.08.033
ISSN: 2211-1247
Type of Material: Journal Article
Journal/Proceeding Title: Cell Reports
Version: Final published version. This is an open access article.

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