Structural investigation of the cold-adapted acylaminoacyl peptidase from Sporosarcina psychrophila by atomistic simulations and biophysical methods

Papaleo, Elena; Parravicini, Federica; Grandori, Rita; Gioia, Luca De; Brocca, Stefania

doi:10.1016/j.bbapap.2014.09.018

Cited by 25 publications

(24 citation statements)

References 99 publications

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“…The data sets comprised 1786 and 3572 mutated variants for monomer and dimer scans, respectively. The distribution of ΔΔG values for the data sets (Figure 5E) is similar to those of other proteins with different folds investigated using the same pipeline (Papaleo et al, 2014a; Mathiassen et al, 2015). The distribution of ΔΔG values for complex formation turned out to be much narrower with values rarely higher than 5 kcal/mol.…”

Section: Resultssupporting

confidence: 70%

“…To obtain a single PSN for each MD ensemble, we included, in the final graph, only those edges which were present in at least 20% of the simulation frames ( p crit = 20%), as previously applied in other cases of study (Papaleo et al, 2012a,b, 2014a; Jónsdóttir et al, 2014; Tiberti et al, 2014; Lambrughi et al, 2016a,b). For each pair of nodes in the PSN graph, a variant of the depth-first search algorithm was employed to identify the shortest path of communication.…”

Section: Methodsmentioning

confidence: 99%

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The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

Nygaard

Terkelsen

Olsen

et al. 2016

Front. Mol. Biosci.

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SCAN domains in zinc-finger transcription factors are crucial mediators of protein-protein interactions. Up to 240 SCAN-domain encoding genes have been identified throughout the human genome. These include cancer-related genes, such as the myeloid zinc finger 1 (MZF1), an oncogenic transcription factor involved in the progression of many solid cancers. The mechanisms by which SCAN homo- and heterodimers assemble and how they alter the transcriptional activity of zinc-finger transcription factors in cancer and other diseases remain to be investigated. Here, we provide the first description of the conformational ensemble of the MZF1 SCAN domain cross-validated against NMR experimental data, which are probes of structure and dynamics on different timescales. We investigated the protein-protein interaction network of MZF1 and how it is perturbed in different cancer types by the analyses of high-throughput proteomics and RNASeq data. Collectively, we integrated many computational approaches, ranging from simple empirical energy functions to all-atom microsecond molecular dynamics simulations and network analyses to unravel the effects of cancer-related substitutions in relation to MZF1 structure and interactions.

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Section: Resultssupporting

confidence: 70%

Section: Methodsmentioning

confidence: 99%

The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

Nygaard

Terkelsen

Olsen

et al. 2016

Front. Mol. Biosci.

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“…We thus estimated the changes in free energy associated to protein stability for each of the LC3B somatic mutations using an empirical energy function (Guerois et al, 2002;Schymkowitz et al, 2005). We implemented this procedure in a high-throughput manner (Nygaard et al, 2016;Papaleo et al, 2014a) so that all the possible mutations at each LC3B site can be assessed. Such high-throughput approach allowed us to evaluate the impact of all possible mutations in the protein without being limited to the mutations found in the cancer genomic studies.…”

Section: Assessment Of the Impact On Protein Stability Upon Lc3b Missmentioning

confidence: 99%

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

Fas

Kumar

Sora

et al. 2019

Preprint

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Autophagy is a cellular process to recycle damaged cellular components and its modulation can be exploited for disease treatments. A key autophagy player is a ubiquitin-like protein, LC3B. Compelling evidence attests the role of autophagy and LC3B in different cancer types. Many LC3B structures have been solved, but a comprehensive study, including dynamics, has not been yet undertaken. To address this knowledge gap, we assessed ten physical models for molecular dynamics for their capabilities to describe the structural ensemble of LC3B in solution using different metrics and comparison with NMR data. With the resulting LC3B ensembles, we characterized the impact of 26 missense mutations from Pan-Cancer studies with different approaches. Our findings shed light on driver or neutral mutations in LC3B, providing an atlas of its modifications in cancer. Our framework could be used to assess the pathogenicity of mutations by accounting for the different aspects of protein structure and function altered by mutational events.

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“…This observation is confirmed by calculation of buried association interface with the program PISA [30], indicating that each subunit covers~1840 A 2 , with an estimated dissociation free energy of 18.3 kcalÁmol À1 . Accordingly, previous dynamic light scattering and native electrospray ionization mass spectrometry experiments indicated that SpAAP in solution is mainly dimeric [19].…”

Section: Novel Quaternary Assemblymentioning

confidence: 97%