@article{88036,
  keywords = {Animals, Molecular Dynamics Simulation, Static Electricity, Crystallography, X-Ray, Protein Structure, Tertiary, Humans, Binding Sites, Protein Binding, Recombinant Fusion Proteins, Mutagenesis, Site-Directed, Mice, Nuclear Proteins, Cell Line, Tumor, Cell Adhesion Molecules, Hydrogen Bonding},
  author = {Feng Guo and Liling Wan and Aiping Zheng and Vitali Stanevich and Yong Wei and Kenneth Satyshur and Minhong Shen and Woojong Lee and Yibin Kang and Yongna Xing},
  title = {Structural insights into the tumor-promoting function of the MTDH-SND1 complex.},
  abstract = {<p>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{\textquoteright}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.</p>
},
  year = {2014},
  journal = {Cell Rep},
  volume = {8},
  pages = {1704-13},
  month = {09/2014},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2014.08.033},
  language = {eng},
}