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Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin ?v?6.

Sorge, Jessica L., Wagstaff, Jane L., Rowe, Michelle L., Williamson, Richard A., Howard, Mark J. (2015) Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin ?v?6. Organic & Biomolecular Chemistry, 13 (29). pp. 8001-8007. ISSN 1477-0520. (doi:10.1039/c5ob01237f) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:49542)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1039/c5ob01237f

Abstract

Integrin ?v?6 is a cell surface arginine-glycine-aspartic acid (RGD)-specific heterodimeric glycoprotein that is only expressed on epithelia during processes of tissue remodelling, including cancer. The specificity and molecular nature of interactions toward this integrin are poorly understood and new insights into such processes are important to cell biologists and pharmaceutical drug discovery. This study demonstrates the application of quantitative two-dimensional saturation transfer (Q2DSTD) NMR to obtain precise details of peptide interactions with integrin ?v?6 and their correlation to specificity for the integrin. This approach highlights subtle but significant differences in ligand contact by three related 21-mer peptides: FMDV2, an ?v?6 specific peptide and DBD1 and LAP2T1 peptides that bind many ?v integrins in addition to ?v?6. FMDV2 and DBD1 differ only by the cyclisation of DBD1; a process that removes ?v?6 specificity. Q2DSTD NMR demonstrates these peptides experience significantly different interactions with the integrin; FMDV contacts primarily through four residues: 6Leu, 10Leu, 12Val and 13Leu, whereas DBD1 and LAP2T1 have more widespread contacts across their sequences. Q2DSTD NMR combined two-dimensional STD with quantitation by considering the relaxation of the ligand (CRL) to provide precise ligand contact information. This study also examines the role of CRL in the Q2DSTD process and how quantitation modifies STD data and unravels epitope-mapping variability to provide precise results that differentiate interactions at the atomic level for each peptide.

Item Type: Article
DOI/Identification number: 10.1039/c5ob01237f
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Susan Davies
Date Deposited: 16 Jul 2015 11:30 UTC
Last Modified: 29 May 2019 14:51 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/49542 (The current URI for this page, for reference purposes)
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