ORCID Profile
0000-0002-9923-8590
Current Organisation
Università degli Studi di Milano
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Publisher: Proceedings of the National Academy of Sciences
Date: 10-09-2018
Abstract: Efficient synthesis and folding of proteins, avoiding misfolded states, are central to cell function. As folding may be initiated in parallel with translation, key experimental challenges are to map changes that occur in folding free energy landscapes as translation proceeds and to understand how these landscapes might be modulated by the ribosome and auxiliary factors. Here, we study the length-dependent folding of a domain from a tandem repeat protein and solve the structure of a stable folding intermediate. Although destabilized by the ribosome at equilibrium, modeling of the nonequilibrium folding pathway nevertheless indicates a significant role for proline isomerization during translation. We develop a simple model to explore the impact of cotranslational folding kinetics on misfolding hazards.
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NSMB.3182
Publisher: Elsevier BV
Date: 2015
Publisher: Proceedings of the National Academy of Sciences
Date: 18-04-2016
Abstract: Protein biosynthesis is carried out by ribosomes, the macromolecular machines present in all kingdoms of life. Aided by molecular chaperones, nascent proteins can begin to fold while emerging from the ribosome. Achieving their native fold, and avoiding misfolding, is thereby crucial for the fate of all newly synthesized proteins. The molecular details of this fundamental process, however, are poorly understood. In this work we develop a combined NMR and molecular simulation approach to characterize the behavior during biosynthesis of α-synuclein (αSyn), an intrinsically disordered protein associated with Parkinson’s disease. The detailed interactions of αSyn with the ribosome surface and with trigger factor, a ribosome-associated chaperone, reveal the first steps of how a nascent chain emerges from the ribosome.
Publisher: Portland Press Ltd.
Date: 07-08-2014
DOI: 10.1042/BJ20131474
Abstract: MBF1 (multi-protein bridging factor 1) is a protein containing a conserved HTH (helix–turn–helix) domain in both eukaryotes and archaea. Eukaryotic MBF1 has been reported to function as a transcriptional co-activator that physically bridges transcription regulators with the core transcription initiation machinery of RNA polymerase II. In addition, MBF1 has been found to be associated with polyadenylated mRNA in yeast as well as in mammalian cells. aMBF1 (archaeal MBF1) is very well conserved among most archaeal lineages however, its function has so far remained elusive. To address this, we have conducted a molecular characterization of this aMBF1. Affinity purification of interacting proteins indicates that aMBF1 binds to ribosomal subunits. On sucrose density gradients, aMBF1 co-fractionates with free 30S ribosomal subunits as well as with 70S ribosomes engaged in translation. Binding of aMBF1 to ribosomes does not inhibit translation. Using NMR spectroscopy, we show that aMBF1 contains a long intrinsically disordered linker connecting the predicted N-terminal zinc-ribbon domain with the C-terminal HTH domain. The HTH domain, which is conserved in all archaeal and eukaryotic MBF1 homologues, is directly involved in the association of aMBF1 with ribosomes. The disordered linker of the ribosome-bound aMBF1 provides the N-terminal domain with high flexibility in the aMBF1–ribosome complex. Overall, our findings suggest a role for aMBF1 in the archaeal translation process.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2019
DOI: 10.1038/S41467-019-09133-W
Abstract: Systemic light chain amyloidosis (AL) is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.0 Å resolution cryo-electron microscopy map and molecular model of amyloid fibrils extracted from the heart of an AL amyloidosis patient with severe amyloid cardiomyopathy. The helical fibrils are composed of a single protofilament, showing typical 4.9 Å stacking and cross-β architecture. Two distinct polypeptide stretches (total of 77 residues) from the LC variable domain (V l ) fit the fibril density. Despite V l high sequence variability, residues stabilizing the fibril core are conserved through different cardiotoxic V l , highlighting structural motifs that may be common to misfolding-prone LCs. Our data shed light on the architecture of LC amyloids, correlate amino acid sequences with fibril assembly, providing the grounds for development of innovative medicines.
Publisher: Springer Science and Business Media LLC
Date: 06-2015
DOI: 10.1038/NSMB.3035
Publisher: Elsevier BV
Date: 10-2009
Publisher: Cold Spring Harbor Laboratory
Date: 17-01-2021
DOI: 10.1101/2021.01.15.426794
Abstract: The inherent flexibility of intrinsically disordered proteins (IDPs) makes it difficult to interpret experimental data using structural models. On the other hand, molecular dynamics simulations of IDPs often suffer from force-field inaccuracies, and long simulations times or enhanced s ling methods are needed to obtain converged ensembles. Here, we apply metainference and Bayesian/Maximum Entropy reweighting approaches to integrate prior knowledge of the system with experimental data, while also dealing with various sources of errors and the inherent conformational heterogeneity of IDPs. We have measured new SAXS data on the protein α -synuclein, and integrate this with simulations performed using different force fields. We find that if the force field gives rise to ensembles that are much more compact than what is implied by the SAXS data it is difficult to recover a reasonable ensemble. On the other hand, we show that when the simulated ensemble is reasonable, we can obtain an ensemble that is consistent with the SAXS data, but also with NMR diffusion and paramagnetic relaxation enhancement data.
Publisher: Public Library of Science (PLoS)
Date: 26-08-2013
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Carlo Camilloni.