All Outputs (54)

HspB1 phosphorylation regulates its intramolecular dynamics and mechanosensitive molecular chaperone interaction with filamin C (2019)
Journal Article
Collier, M. P., Alderson, T. R., de Villiers, C. P., Nicholls, D., Gastall, H. Y., Allison, T. M., Degiacomi, M. T., Jiang, H., Mlynek, G., Fürst, D. O., van der Ven, P. F., Djinovic-Carugo, K., Baldwin, A. J., Watkins, H., Gehmlich, K., & Benesch, J. L. (2019). HspB1 phosphorylation regulates its intramolecular dynamics and mechanosensitive molecular chaperone interaction with filamin C. Science Advances, 5(5), Article eaav8421. https://doi.org/10.1126/sciadv.aav8421

Mechanical force–induced conformational changes in proteins underpin a variety of physiological functions, typified in muscle contractile machinery. Mutations in the actin-binding protein filamin C (FLNC) are linked to musculo- skeletal pathologies c... Read More about HspB1 phosphorylation regulates its intramolecular dynamics and mechanosensitive molecular chaperone interaction with filamin C.

Coupling Molecular Dynamics and Deep Learning to Mine Protein Conformational Space (2019)
Journal Article
Degiacomi, M. T. (2019). Coupling Molecular Dynamics and Deep Learning to Mine Protein Conformational Space. Structure, 27(6), 1034-1040.e3. https://doi.org/10.1016/j.str.2019.03.018

Flexibility is often a key determinant of protein func- tion. To elucidate the link between their molecular structure and role in an organism, computational techniques such as molecular dynamics can be leveraged to characterize their conformational s... Read More about Coupling Molecular Dynamics and Deep Learning to Mine Protein Conformational Space.

Structural and functional consequences of age-related isomerization in α-crystallins (2019)
Journal Article
Lyon, Y. A., Collier, M. P., Riggs, D. L., Degiacomi, M. T., Benesch, J. L., & Julian, R. R. (2019). Structural and functional consequences of age-related isomerization in α-crystallins. Journal of Biological Chemistry, 294(19), 7546-7555. https://doi.org/10.1074/jbc.ra118.007052

Long-lived proteins are subject to spontaneous degradation and may accumulate a range of modifications over time, including subtle alterations such as side-chain isomerization. Recently, tandem MS has enabled identification and characterization of su... Read More about Structural and functional consequences of age-related isomerization in α-crystallins.

It takes a dimer to tango: Oligomeric small heat shock proteins dissociate to capture substrate (2018)
Journal Article
Santhanagopalan, I., Degiacomi, M. T., Shepherd, D. A., Hochberg, G. K., Benesch, J. L., & Vierling, E. (2018). It takes a dimer to tango: Oligomeric small heat shock proteins dissociate to capture substrate. Journal of Biological Chemistry, 293(51), 19511-19521. https://doi.org/10.1074/jbc.ra118.005421

Small heat-shock proteins (sHsps) are ubiquitous molecular chaperones, and sHsp mutations or altered expression are linked to multiple human disease states. sHsp monomers assemble into large oligomers with dimeric substructure, and the dynamics of sH... Read More about It takes a dimer to tango: Oligomeric small heat shock proteins dissociate to capture substrate.

The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons (2018)
Journal Article
Finelli, M. J., Aprile, D., Castroflorio, E., Jeans, A., Moschetta, M., Chessum, L., Degiacomi, M. T., Grasegger, J., Lupien-Meilleur, A., Bassett, A., Rossignol, E., Campeau, P. M., Bowl, M. R., Benfenati, F., Fassio, A., & Oliver, P. L. (2019). The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons. Human Molecular Genetics, 28(4), 584-597. https://doi.org/10.1093/hmg/ddy370

Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, onychodystrophy, osteod... Read More about The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons.

Lipid binding attenuates channel closure of the outer membrane protein OmpF (2018)
Journal Article
Liko, I., Degiacomi, M. T., Lee, S., Newport, T. D., Gault, J., Reading, E., …Robinson, C. V. (2018). Lipid binding attenuates channel closure of the outer membrane protein OmpF. Proceedings of the National Academy of Sciences, 115(26), 6691-6696. https://doi.org/10.1073/pnas.1721152115

Strong interactions between lipids and proteins occur primarily through association of charged headgroups and amino acid side chains, rendering the protonation status of both partners important. Here we use native mass spectrometry to explore lipid b... Read More about Lipid binding attenuates channel closure of the outer membrane protein OmpF.

On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies (2018)
Journal Article
Degiacomi, M. T. (2019). On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies. Journal of The American Society for Mass Spectrometry, 30(1), 113-117. https://doi.org/10.1007/s13361-018-1974-2

Ion mobility mass spectrometry (IM/MS) can provide structural information on intact protein complexes. Such data, including connectivity and collision cross sections (CCS) of assemblies’ subunits, can in turn be used as a guide to produce representat... Read More about On the Effect of Sphere-Overlap on Super Coarse-Grained Models of Protein Assemblies.

Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions (2018)
Journal Article
Hochberg, G. K., Shepherd, D. A., Marklund, E. G., Santhanagoplan, I., Degiacomi, M. T., Laganowsky, A., …Benesch, J. L. (2018). Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions. Science, 359(6378), 930-935. https://doi.org/10.1126/science.aam7229

Oligomeric proteins assemble with exceptional selectivity, even in the presence of closely related proteins, to perform their cellular roles. We show that most proteins related by gene duplication of an oligomeric ancestor have evolved to avoid heter... Read More about Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.

Mineral Surface Chemistry Control for Origin of Prebiotic Peptides (2017)
Journal Article
Erastova, V., Degiacomi, M. T., Fraser, D., & Greenwell, H. C. (2017). Mineral Surface Chemistry Control for Origin of Prebiotic Peptides. Nature Communications, 8, Article 2033. https://doi.org/10.1038/s41467-017-02248-y

Some seventy years ago, John Desmond Bernal proposed a role for clays in the origin of life. While much research has since been dedicated to the study of silicate clays, layered double hydroxides, believed to be common on the early Earth, have receiv... Read More about Mineral Surface Chemistry Control for Origin of Prebiotic Peptides.

Accommodating protein dynamics in the modeling of chemical crosslinks (2017)
Journal Article
Degiacomi, M. T., Schmidt, C., Baldwin, A. J., & Benesch, J. L. (2017). Accommodating protein dynamics in the modeling of chemical crosslinks. Structure, 25(11), 1751-1757.e5. https://doi.org/10.1016/j.str.2017.08.015

Chemical crosslinking can identify the neighborhood relationships between specific amino-acid residues in proteins. The interpretation of crosslinking data is typically performed using single, static atomic structures. However, proteins are dynamic,... Read More about Accommodating protein dynamics in the modeling of chemical crosslinks.

Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory (2017)
Journal Article
Pritišanac, I., Degiacomi, M., Alderson, T., Carneiro, M., Ab, E., Siegal, G., & Baldwin, A. J. (2017). Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory. Journal of the American Chemical Society, 139(28), 9523-9533. https://doi.org/10.1021/jacs.6b11358

Methyl groups are powerful probes for the analysis of structure, dynamics and function of supramolecular assemblies, using both solution- and solid-state NMR. Widespread application of the methodology has been limited due to the challenges associated... Read More about Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory.

The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans (2017)
Journal Article
Hopper, J., Ambrose, S., Grant, O., Krumm, S., Allison, T., Degiacomi, M., …Struwe, W. (2017). The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans. Structure, 25(5), 773-782.e5. https://doi.org/10.1016/j.str.2017.03.015

Select lectins have powerful anti-viral properties that effectively neutralize HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the mechanism by which one of the most potent lectins, BanLec, achieves its inhibition. We identif... Read More about The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans.

Disentangling constraints using viability evolution principles in integrative modeling of macromolecular assemblies (2017)
Journal Article
Tamò, G., Maesani, A., Träger, S., Degiacomi, M., Floreano, D., & Dal Peraro, M. (2017). Disentangling constraints using viability evolution principles in integrative modeling of macromolecular assemblies. Scientific Reports, 7(1), Article 235. https://doi.org/10.1038/s41598-017-00266-w

Predicting the structure of large molecular assemblies remains a challenging task in structural biology when using integrative modeling approaches. One of the main issues stems from the treatment of heterogeneous experimental data used to predict the... Read More about Disentangling constraints using viability evolution principles in integrative modeling of macromolecular assemblies.

Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters (2017)
Journal Article
Landreh, M., Marklund, E., Uzdavinys, P., Degiacomi, M., Coincon, M., Gault, J., …Robinson, C. (2017). Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters. Nature Communications, 8, Article 13993. https://doi.org/10.1038/ncomms13993

Na+/H+ antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the con... Read More about Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters.

Understanding surface interactions in aqueous miscible organic solvent treated layered double hydroxides (2016)
Journal Article
Erastova, V., Degiacomi, M. T., O'Hare, D., & Greenwell, H. C. (2017). Understanding surface interactions in aqueous miscible organic solvent treated layered double hydroxides. RSC Advances, 7(9), 5076-5083. https://doi.org/10.1039/c6ra26834j

Layered materials are of interest for use in a wealth of technological applications, many of which require a high surface area for optimal properties and performance. Recently, an industrially scalable method to create high surface area layered doubl... Read More about Understanding surface interactions in aqueous miscible organic solvent treated layered double hydroxides.

Dimer interface of Bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding (2016)
Journal Article
Liko, I., Degiacomi, M., Mohammed, S., Yoshikawa, S., Schmidt, C., & Robinson, C. (2016). Dimer interface of Bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding. Proceedings of the National Academy of Sciences, 113(29), 8230-8235. https://doi.org/10.1073/pnas.1600354113

Bovine cytochrome c oxidase is an integral membrane protein complex comprising 13 protein subunits and associated lipids. Dimerization of the complex has been proposed; however, definitive evidence for the dimer is lacking. We used advanced mass spec... Read More about Dimer interface of Bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding.

Easy creation of polymeric systems for molecular dynamics with Assemble! (2016)
Journal Article
Degiacomi, M., Erastova, V., & Wilson, M. (2016). Easy creation of polymeric systems for molecular dynamics with Assemble!. Computer Physics Communications, 202, 304-309. https://doi.org/10.1016/j.cpc.2015.12.026

We present Assemble!, a program greatly simplifying the preparation of molecular dynamics simulations of polymeric systems. The program is controlled either via command line or an intuitive Graphical User Interface, and runs on all major operating sy... Read More about Easy creation of polymeric systems for molecular dynamics with Assemble!.

Characterisation of Shigella Spa33 and Thermotoga FliM/N reveals a new model for C-ring assembly in T3SS (2015)
Journal Article
Mcdowell, M., Marcoux, J., Mcvicker, G., Johnson, S., Fong, Y., Stevens, R., …Lea, S. (2016). Characterisation of Shigella Spa33 and Thermotoga FliM/N reveals a new model for C-ring assembly in T3SS. Molecular Microbiology, 99(4), 749-766. https://doi.org/10.1111/mmi.13267

Flagellar type III secretion systems (T3SS) contain an essential cytoplasmic-ring (C-ring) largely composed of two proteins FliM and FliN, whereas an analogous substructure for the closely related non-flagellar (NF) T3SS has not been observed in situ... Read More about Characterisation of Shigella Spa33 and Thermotoga FliM/N reveals a new model for C-ring assembly in T3SS.

EM∩IM: Software for relating ion mobility mass spectrometry and electron microscopy data (2015)
Journal Article
Degiacomi, M., & Benesch, J. (2016). EM∩IM: Software for relating ion mobility mass spectrometry and electron microscopy data. Analyst, 141(1), 70-75. https://doi.org/10.1039/c5an01636c

We present EM∩IM, software that allows the calculation of collision cross-sections from electron density maps obtained for example by means of transmission electron microscopy. This allows the assessment of structures other than those described by at... Read More about EM∩IM: Software for relating ion mobility mass spectrometry and electron microscopy data.

A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis (2015)
Journal Article
Marcoux, J., Mangione, P., Porcari, R., Degiacomi, M., Verona, G., Taylor, G., …Bellotti, V. (2015). A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. EMBO Molecular Medicine, 7(10), 1337-1349. https://doi.org/10.15252/emmm.201505357

The mechanisms underlying transthyretin‐related amyloidosis in vivo remain unclear. The abundance of the 49–127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and relea... Read More about A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis.