PyXlinkViewer: a flexible tool for visualisation of protein chemical crosslinking data within the PyMOL molecular graphics system

Schiffrin, Bob; Radford, Sheena E.; Brockwell, David J.; Calabrese, Antonio N.

doi:10.1101/2020.06.16.154773

Cited by 45 publications

(49 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…306 In addition to LPS-containing systems, simulations of the OMP β-barrel domains in phospholipid bilayers of various tail lengths revealed hydrophobic mismatch induced lipid sorting or membrane disruption around the β-barrel structures. 308,309 Moreover, the tilting motion of the β-barrel from the lipid A acylase PagP was found to facilitate the access of lipid acyl chains into the mouth of the central binding pocket. 310 The two-domain homology model of PmOmpA is composed of a transmembrane β-barrel domain as well as a periplasmic α-helical domain.…”

Section: 11mentioning

confidence: 99%

Characterization of Lipid–Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation

et al. 2019

View full text Add to dashboard Cite

The cellular membrane constitutes one of the most fundamental compartments of a living cell, where key processes such as selective transport of material and exchange of information between the cell and its environment are mediated by proteins that are closely associated with the membrane. The heterogeneity of lipid composition of biological membranes and the effect of lipid molecules on the structure, dynamics, and function of membrane proteins are now widely recognized. Characterization of these functionally important lipid-protein interactions with experimental techniques is however still prohibitively challenging. Molecular dynamics (MD) simulations offer a powerful complementary approach with sufficient temporal and spatial resolutions to gain atomic-level structural information and energetics on lipid-protein interactions. In this review, we aim to provide a broad survey of MD simulations focusing on exploring lipidprotein interactions and characterizing lipid-modulated protein structure and dynamics that have been successful in providing novel insight into the mechanism of membrane protein function.

show abstract

Section: 11mentioning

confidence: 99%

Characterization of Lipid–Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The distribution of the cross-links on the MjGATase and MjATPPase protein sequences was visualized using xiVIEW web server. 59 The cross-links were visualized in the MjGATase and MjATPPase/XMP crystal structures and the Euclidean distances between the Cα atoms of the cross-linked residues were measured using the PyXlinkViewer plugin 60 for PyMOL. 61…”

Section: Identification Of Cross-linked Residuesmentioning

confidence: 99%

Mechanistic insights into the functioning of GMP synthetase: a two-subunit, allosterically regulated, ammonia tunnelling enzyme

Shivakumaraswamy

Kumar

Bellur

et al. 2022

Preprint

View full text Add to dashboard Cite

Guanosine 5'-monophosphate (GMP) synthetases, enzymes that catalyze the conversion of xanthosine 5'-monophosphate (XMP) to GMP are comprised of two different catalytic units, which are either two domains of a polypeptide chain or two subunits that associate to form a complex. The glutamine amidotransferase (GATase) unit hydrolyzes glutamine generating ammonia and the ATP pyrophosphatase (ATPPase) unit catalyzes the formation of AMP-XMP intermediate. The substrate-bound ATPPase allosterically activates GATase and the ammonia thus generated is tunnelled to the ATPPase active site where it reacts with AMP-XMP generating GMP. In ammonia tunnelling enzymes reported thus far, a tight complex of the two subunits is observed, while the interaction of the two subunits of Methanocaldococcus jannaschii GMP synthetase (MjGMPS) is transient with the underlying mechanism of allostery and substrate channelling largely unclear. Here, we present a mechanistic model encompassing the various steps in the catalytic cycle of MjGMPS based on biochemical experiments, crystal structure and cross-linking mass spectrometry guided integrative modelling. pH dependence of enzyme kinetics establish that ammonia is tunnelled across the subunits with the lifetime of the complex being ≤ 0.5 s. The crystal structure of XMP-bound ATPPase subunit reported herein highlights the role of conformationally dynamic loops in enabling catalysis. The structure of MjGMPS derived using restraints obtained from cross-linking mass spectrometry has enabled the visualization of subunit interactions that enable allostery under catalytic conditions. We integrate the results and propose a functional mechanism for MjGMPS detailing the various steps involved in catalysis.

show abstract

“…The simplest way to visualize crosslinking-MS data in a structural context has been to map residue-residue pairs onto structures as Euclidean distances in a visualization software such as ChimeraX (Pettersen et al, 2021), PyMOL (Schiffrin et al, 2020), or Chimera (Pettersen et al, 2004), where the plugin Xlink Analyzer provides a framework for the inspection of crosslinking-MS data (Kosinski et al, 2015). This simple approach is certainly powerful and allows the user to observe the most salient features of the data, such as whether a protein fold or a particular protein-protein interface is broadly compatible with the detected crosslinks (Figure 3).…”

Section: Crosslinking-ms In Structural Biology: (1) Visualization Model Building and Model Validationmentioning

confidence: 99%

Leveraging crosslinking mass spectrometry in structural and cell biology

Graziadei

Rappsilber

2022

Structure

View full text Add to dashboard Cite

Crosslinking mass spectrometry (crosslinking-MS) is a versatile tool providing structural insights into protein conformation and protein-protein interactions. Its medium-resolution residue-residue distance restraints have been used to validate protein structures proposed by other methods and have helped derive models of protein complexes by integrative structural biology approaches. The use of crosslinking-MS in integrative approaches is underpinned by progress in estimating error rates in crosslinking-MS data and in combining these data with other information. The flexible and high-throughput nature of crosslinking-MS has allowed it to complement the ongoing resolution revolution in electron microscopy by providing system-wide residue-residue distance restraints, especially for flexible regions or systems. Here, we review how crosslinking-MS information has been leveraged in structural model validation and integrative modeling. Crosslinking-MS has also been a key technology for cell biology studies and structural systems biology where, in conjunction with cryoelectron tomography, it can provide structural and mechanistic insights directly in situ. ll

show abstract

PyXlinkViewer: a flexible tool for visualisation of protein chemical crosslinking data within the PyMOL molecular graphics system

Cited by 45 publications

References 38 publications

Characterization of Lipid–Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation

Characterization of Lipid–Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation

Mechanistic insights into the functioning of GMP synthetase: a two-subunit, allosterically regulated, ammonia tunnelling enzyme

Leveraging crosslinking mass spectrometry in structural and cell biology

Contact Info

Product

Resources

About