Please use this identifier to cite or link to this item:
|Title:||Structural and functional analysis of phosphothreonine-dependent FHA domain interactions|
|Citation:||Pennell, S., Westcott, S., Ortiz-Lombardía, M., Patel, D., Li, J., Nott, T.J., Mohammed, D., Buxton, R.S., Yaffe, M.B., Verma, C., Smerdon, S.J. (2010-12-08). Structural and functional analysis of phosphothreonine-dependent FHA domain interactions. Structure 18 (12) : 1587-1595. ScholarBank@NUS Repository. https://doi.org/10.1016/j.str.2010.09.014|
|Abstract:||FHA domains are well established as phospho-dependent binding modules mediating signal transduction in Ser/Thr kinase signaling networks in both eukaryotic and prokaryotic species. Although they are unique in binding exclusively to phosphothreonine, the basis for this discrimination over phosphoserine has remained elusive. Here, we attempt to dissect overall binding specificity at the molecular level. We first determined the optimal peptide sequence for Rv0020c FHA domain binding by oriented peptide library screening. This served as a basis for systematic mutagenic and binding analyses, allowing us to derive relative thermodynamic contributions of conserved protein and peptide residues to binding and specificity. Structures of phosphopeptide-bound and uncomplexed Rv0020c FHA domain then directed molecular dynamics simulations which show how the extraordinary discrimination in favor of phosphothreonine occurs through formation of additional hydrogen-bonding networks that are ultimately stabilized by van der Waals interactions of the phosphothreonine γ-methyl group with a conserved pocket on the FHA domain surface. © 2010 Elsevier Ltd. All rights reserved.|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Nov 16, 2018
WEB OF SCIENCETM
checked on Nov 22, 2017
checked on Oct 5, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.