Structural insights into the tumor-promoting function of the MTDH-SND1 complex

Feng Guo, Liling Wan, Aiping Zheng, Vitali Stanevich, Yong Wei, Kenneth A. Satyshur, Minhong Shen, Woojong Lee, Yibin Kang, Yongna Xing

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1704-1713
Number of pages10
JournalCell Reports
Volume8
Issue number6
DOIs
StatePublished - Sep 25 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Guo, F., Wan, L., Zheng, A., Stanevich, V., Wei, Y., Satyshur, K. A., Shen, M., Lee, W., Kang, Y., & Xing, Y. (2014). Structural insights into the tumor-promoting function of the MTDH-SND1 complex. Cell Reports, 8(6), 1704-1713. https://doi.org/10.1016/j.celrep.2014.08.033