4QMG

The Structure of MTDH-SND1 Complex Reveals Novel Cancer-Promoting Interactions

Summary for 4QMG

• Entry DOI: 10.2210/pdb4qmg/pdb
• Related: 2E6N 2HQE 2HQX 3BDL 3OMC 3OMG
• Descriptor: Staphylococcal nuclease domain-containing protein 1, Protein LYRIC, SULFATE ION, ... (6 entities in total)
• Functional Keywords: sn domains, oligonucleotide/oligosaccharide binding-fold (ob-fold), dna/rna-binding, mirna-mediated silencing, nuclease, breast cancer, tumorigenesis, snd1, mtdh, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q7KZF4; Endoplasmic reticulum membrane; Single-pass membrane protein: Q86UE4
• Total number of polymer chains: 10
• Total formula weight: 208065.20

Authors

Guo, F.,Stanevich, V.,Wan, L.,Satyshur, K.,Kang, Y.,Xing, Y. (deposition date: 2014-06-16, release date: 2014-10-08, Last modification date: 2024-11-20)

Primary citation

Guo, F.,Wan, L.,Zheng, A.,Stanevich, V.,Wei, Y.,Satyshur, K.A.,Shen, M.,Lee, W.,Kang, Y.,Xing, Y.
Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex.
Cell Rep, 8:1704-1713, 2014

PubMed 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.

PubMed: 25242325
DOI: 10.1016/j.celrep.2014.08.033

Experimental method

X-RAY DIFFRACTION (2.701 Å)