A scoring model for phosphopeptide site localization and its impact on the question of whether to use MSA

Fischer, Juliana de Saldanha da Gama; Santos, Marlon D.M.; Marchini, Fabrício Klerynton; Barbosa, Valmir C.; Carvalho, Paulo C.; Zanchin, Nilson Ivo Tonin

doi:10.1016/j.jprot.2015.01.008

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…It is important to note that the precise O-glycosylation site assignation is hampered by the fact that collision energies used for peptide fragmentation cause the breakage of the weaker O-glycosydic bond leaving behind mostly unmodified fragments. Although the glycosylation site assignation was not the aim of our study, the utility XDScoring of Patternlab for proteomics developed for statistical phosphopeptide site localization [58], was preliminary tested in our data. Glycosylation site p-value is presented in S6 Table.…”

Section: Resultsmentioning

confidence: 99%

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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21 Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium 22 tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted 23 and cell wall proteins interact with the host and play important roles in pathogenicity. These 24 proteins have been explored as candidate diagnostic markers, potential drug targets or vaccine 25 antigens, and special attention has been given to the role of their post-translational 26 modifications. With the purpose of contributing to the proteomic characterization of this 27 important pathogen including an O-glycosylation profile analysis, we performed a shotgun 28 analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass 29 spectrometry and a label-free spectral counting normalization approach for protein 30 quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the 31 most abundant proteins belong to the extracellular region or cell wall compartment, and that 32 the functional categories with higher protein abundance factor were virulence, detoxification 33 and adaptation, and cell wall and cell processes. In culture filtrate, 140 proteins were predicted 34 to contain one of the three types of bacterial N-terminal signal peptides. Besides, various 35 proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the 36 type VII secretion system using nonclassical secretion signals, were also identified. O-37 glycosylation was identified as a frequent modification, being present in 108 proteins, principally 38 lipoproteins and secreted immunogenic antigens. We could identify a group of proteins 39 consistently detected in previous studies, most of which were highly abundant proteins. 40 Interestingly, we also provide proteomic evidence for 62 novel O-glycosylated proteins, aiding 41 to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. 48 HIV-positive people [1]. Although TB diagnosis and successful treatment averts millions of 49 deaths each year, there are still large and persistent gaps related to this infection that must be 50 resolved in order to accelerate progress towards the goal of ending the TB epidemic endorsed 51 by WHO [1]. 52 M. tuberculosis (MTB), has evolved successful mechanisms to circumvent the hostile 53 environment of the macrophage, such as inhibiting the phagosome-lysosome fusion and to 54 escape the acidic environment inside the phagolysosome [2]. MTB may be unique in its ability 55 to exploit adaptive immune responses, through inflammatory lung tissue damage, to promote 56 its transmission [3]. It has been proposed that this microorganism was pressed by an 57 evolutionary selection that resulted in an infection that induces partial immunity, where the 58 host survives a long period after being infected with the pathogen, aiding in microorganism 59 persistence and transmission [3]. MTB mechanisms of evasion of host immune system were 60 proposed to have c...

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Section: Resultsmentioning

confidence: 99%

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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“…A search engine independent version has been published recently [62]. MD-Scores goes a step further and infers a probabilistic function from the distribution of these independent scores and assigns a data set specific statistical confidence [63]. PTM score is part of the Andromeda of MaxQuant [64].…”

Section: False Localization Ratementioning

confidence: 99%

Computational and statistical methods for high-throughput analysis of post-translational modifications of proteins

Schwämmle

Verano‐Braga

Roepstorff

2015

Journal of Proteomics

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“…Accurate identification of the phosphorylation site within a peptide is also a challenge since mis-assignment can occur when there are multiple phosphorylatable residues close to each other within a peptide. The use of powerful scoring algorithms and the development of fragmentation strategies such as MSA (MultiStage Activation) which invokes MS3, considerably decreases this risk, even if it requires longer data acquisition time 14 , 15 . More recently, the quantification of specific proteins in biological samples based on selected reaction monitoring (SRM) is emerging as a targeted phosphoproteomic approach and this will help us define the relevance of site-specific phosphorylation events 16 .…”

Section: Introductionmentioning

confidence: 99%

Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes

Adam

Hunter

2018

Laboratory Investigation

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Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell’s proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues – pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu, and pCys. Most of the effort in studying protein phosphorylation has been focused on Ser, Thr and Tyr phosphorylation. The recent development of 1- and 3-pHis monoclonal antibodies promises to increase our understanding of His phosphorylation and the kinases and phosphatases involved. Several His kinases are well defined in prokaryotes, especially those involved in Two-Component System (TCS) signaling. However in higher eukaryotes, NM23, a protein originally characterized as a nucleoside diphosphate kinase, is the only characterized protein-histidine kinase. This ubiquitous and conserved His kinase autophosphorylates its active site His, and transfers this phosphate either onto a nucleoside diphosphate or onto a protein His residue. Studies of NM23 protein targets using newly developed anti-pHis antibodies will surely help illuminate the elusive His phosphorylation-based signaling pathways. This review discusses the role that the NM23/NME/NDPK phosphotransferase plays, how the addition of the pHis phosphoproteome will expand the phosphoproteome, and make His phosphorylation part of the global phosphorylation world. It also summarizes why our understanding of phosphorylation is still largely restricted to the acid stable phosphoproteome, and highlights the study of NM23 histidine kinase as an entrée into the world of histidine phosphorylation.

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A scoring model for phosphopeptide site localization and its impact on the question of whether to use MSA

Cited by 9 publications

References 38 publications

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Computational and statistical methods for high-throughput analysis of post-translational modifications of proteins

Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes

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