Structural interrogation of phosphoproteome identified by mass spectrometry reveals allowed and disallowed regions of phosphoconformation
Somavarapu, Arun Kumar and Balakrishnan, Satish and Gautam, Amit Kumar Singh and Palmer, David and Venkatraman, Prasanna (2014) Structural interrogation of phosphoproteome identified by mass spectrometry reveals allowed and disallowed regions of phosphoconformation. BMC Structural Biology, 14 (9). (https://doi.org/10.1186/1472-6807-14-9)
Preview |
PDF.
Filename: 1472_6807_14_9.pdf
Final Published Version License: Download (2MB)| Preview |
Abstract
High-throughput mass spectrometric (HT-MS) study is the method of choice for monitoring global changes in proteome. Data derived from these studies are meant for further validation and experimentation to discover novel biological insights. Here we evaluate use of relative solvent accessible surface area (rSASA) and DEPTH as indices to assess experimentally determined phosphorylation events deposited in PhosphoSitePlus. Based on accessibility, we map these identifications on allowed (accessible) or disallowed (inaccessible) regions of phosphoconformation. Surprisingly a striking number of HT- MS/MS derived events (1461/5947 sites or 24.6%) are present in the disallowed region of conformation. By considering protein dynamics, autophosphorylation events and/or the sequence specificity of kinases, 13.8% of these phosphosites can be moved to the allowed region of conformation. We also demonstrate that rSASA values can be used to increase the confidence of identification of phosphorylation sites within an ambiguous MS dataset. While MS is a stand-alone technique for the identification of vast majority of phosphorylation events, identifications within disallowed region of conformation will benefit from techniques that independently probe for phosphorylation and protein dynamics. Our studies also imply that trapping alternate protein conformations may be a viable alternative to the design of inhibitors against mutation prone drug resistance kinases.
ORCID iDs
Somavarapu, Arun Kumar, Balakrishnan, Satish, Gautam, Amit Kumar Singh, Palmer, David ORCID: https://orcid.org/0000-0003-4356-9144 and Venkatraman, Prasanna;-
-
Item type: Article ID code: 47187 Dates: DateEvent2014Published11 March 2014Published OnlineSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 13 Mar 2014 11:33 Last modified: 31 Oct 2024 01:37 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/47187