Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy

Biochemical and Biophysical Research Communications
Nirosha GunasekaraJudith Hugh

Abstract

Breast cancer causes death through cancer cell migration and subsequent metastasis to distant organs. In vitro, the MUC1 mucin can mediate breast cancer cell migration by binding to intercellular adhesion molecule-1 (ICAM-1). This migration is dependent on MUC1 cytoplasmic domain (MUC1-CD) activation of the non-receptor tyrosine kinase, Src, possibly through competitive displacement of an inhibitory Src intramolecular SH3 binding. Therefore, we characterized the binding site and affinity of the MUC1-CD for Src-SH3 using multidimensional nuclear magnetic resonance (NMR) spectroscopy to monitor the titration of the (15)N labeled Src-SH3 domain with synthetic native and mutant peptides of MUC1-CD. The results revealed that the dissociation constant (K(d)) for the interaction of the native MUC1-CD peptides and Src-SH3 domain was weak with a K(d) of 2-3 mM. Notably, the SH3 residues most perturbed upon peptide binding were located outside the usual hydrophobic binding cleft in a previously described alternate binding site on the Src-SH3, suggesting that MUC1-CD binds to a non-canonical site. The binding characteristics outlined here suggest that the interaction between Src-SH3 and MUC1-CD represents a novel weak electrostatic intera...Continue Reading

References

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May 22, 2002·Biochimica Et Biophysica Acta·Margaret C Frame
Jun 1, 2004·The Journal of Biological Chemistry·Jennifer J RahnJudith C Hugh
Dec 2, 2005·Clinical & Experimental Metastasis·Jennifer J RahnJudith C Hugh
Aug 1, 2006·Trends in Biotechnology·Yugong ChengA Keith Dunker
May 15, 2007·The Journal of Biological Chemistry·Yumei LengDonald Kufe
Feb 18, 2009·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Larry F EllisonUNKNOWN Canadian Cancer Society's Steering Committee for Canadian Cancer Statistics

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Citations

Apr 25, 2013·Progress in Nuclear Magnetic Resonance Spectroscopy·Lu-Yun Lian
Aug 22, 2015·Cellular and Molecular Life Sciences : CMLS·Vasso ApostolopoulosSharron E Gargosky
Mar 29, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Yen-Ting TungShie-Liang Hsieh
Mar 12, 2015·Clinical & Experimental Metastasis·Lacey Haddon, Judith Hugh

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