Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ

Cappelletti, Valentina; Hauser, Thomas; Piazza, Ilaria; Pepelnjak, Monika; Malinovska, Liliana; Fuhrer, Tobias; Li, Yaozong; Dörig, Christian; Boersema, Paul J.; Gillet, Ludovic; Großbach, Jan; Dugourd, Aurélien; Sáez-Rodríguez, Julio; Beyer, Andreas; Zamboni, Nicola; Caflisch, Amedeo; Souza, Natalie de; Picotti, Paola

doi:10.1016/j.cell.2020.12.021

Cited by 105 publications

(97 citation statements)

References 103 publications

(139 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many MS-based techniques, such as cross-linking MS, limited proteolysis, and hydrogen-deuterium exchange MS, proved that MS can effectively provide information about protein structure (Iacobucci et al, 2018;Schopper et al, 2017;Yan and Maier, 2009) and push the MS capacity beyond the determination of protein abundance. To determine protein functional alterations and regulatory events, protein structural data have been shown to be complementary to protein abundance (Cappelletti et al, 2020). Similarly, we suggest that the functional relevance of a phosphorylation site can be determined by combining alterations at the protein structure and abundance level.…”

Section: Discussionmentioning

confidence: 94%

Structural analysis of mammalian protein phosphorylation at a proteome level

2021

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 94%

Structural analysis of mammalian protein phosphorylation at a proteome level

2021

View full text Add to dashboard Cite

show abstract

“…Given the large number of TFs that have phosphosites of unknown function (Figure 2A), an intriguing question arises as to what extent context-specific functions and interactions of TFs are driven by PTMs of the TF itself. Recent advances in structural proteomics technologies that can measure proteome-wide changes in protein structures upon signal induction (Cappelletti et al, 2021) may help answer this question.…”

Section: Regulation Of Tf-binding To Chromatin Through Dna-sequence and Epigeneticsmentioning

confidence: 99%

Transcription factors: Bridge between cell signaling and gene regulation

et al. 2021

View full text Add to dashboard Cite

Transcription factors (TFs) are key regulators of intrinsic cellular processes, such as differentiation and development, and of the cellular response to external perturbation through signaling pathways. In this review we focus on the role of TFs as a link between signaling pathways and gene regulation. Cell signaling tends to result in the modulation of a set of TFs that then lead to changes in the cell's transcriptional programme. We highlight the molecular layers at which TF activity can be measured and the associated technical and conceptual challenges. These layers include post-translational modifications of the TF, regulation of TF binding to DNA through chromatin accessibility and epigenetics, and expression of target genes. We highlight that a large number of TFs are understudied in both signaling and gene regulation studies, and that our knowledge about known TF targets has a strong literature bias. We argue that TFs serve as a perfect bridge between the fields of gene regulation and signaling, and that separating these fields hinders our understanding of cell functions. Multiomics approaches that measure multiple dimensions of TF activity are ideally suited to study the interplay of cell signaling and gene regulation using TFs as the anchor to link the two fields.

show abstract

“…LiP signals that are localized in active sites of metabolic enzymes or protein kinases are associated with metabolite binding events with regulatory function. Structural changes measured with LiP peptides correlate with known variations of activity of signalling pathways, phosphorylation events or metabolic fluxes and are therefore a proxy of functionally relevant events (Cappelletti et al, 2021). As more LiP-MS and TPP datasets profiling different processes and diseases become available, we envision the use of machinelearning approaches to identify which structural features of proteins have regulatory relevance and, in the long term, to prioritize functional sites in a context-specific manner.…”

Section: Expanding the Functional Proteomics Landscape With Biophysics Proteomicsmentioning

confidence: 99%

The rise of proteome‐wide biophysics

Mateus

Savitski

Piazza

2021

Molecular Systems Biology

Self Cite

View full text Add to dashboard Cite

he ultimate goal of proteomics is to provide a holistic view of the biological processes that explain phenotypes. To this end, proteomics approaches have been frequently used to map protein expression in multiple experimental conditions and to identify protein-protein interactions. While informative to a certain extent, protein amounts and physical protein associations do not provide a full picture of protein function. Here, we highlight the novel insights that are made possible in biology and medicine by structural and stability proteomic technologies.

show abstract

Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ

Cited by 105 publications

References 103 publications

Structural analysis of mammalian protein phosphorylation at a proteome level

Structural analysis of mammalian protein phosphorylation at a proteome level

Transcription factors: Bridge between cell signaling and gene regulation

The rise of proteome‐wide biophysics

Contact Info

Product

Resources

About