Protein crystallography lab.

Gallery: Protein crystallography lab.

Facility manager: Dr. Veronika Harmat

Members: Dr. Zsolt Dürvanger, István Bódy, Csaba Hegedűs, Dr. Veronika Harmat, Kevin Zsolt Simon , Máté Sulyok-Eiler , Dr. Dóra K. Menyhárd , Anna J. Kiss-Szemán, PhD

For a better understanding of function and interactions of biological macromolecules, 3D-structure is required at an atomic resolution, typically determined by protein crystallography; a perfect method of choice. On the other hand, small molecular crystallographic studies explore the structural basis of physical-chemical characteristics of the compound. In 2018. new X-ray crystallographic instruments were installed in the EU 2020 framework (Széchenyi 2020*). The aim of these consortial projects is to establish an infrastructure serving as an open lab for a wider range of research groups (ELTE-CrystalLAB). The Rigaku XtaLAB Synergy-R X-ray diffractometer is capable for small molecular and protein crystallographic data collection as well as in situ crystal testing. A TTP Labtech Mosquito-LCP is available for automated crystallization, and monitoring crystal growth is carried out by a Formulatrix Rock Imager 2 system.

*The research within project No. VEKOP-2.3.3-15-2017-00018 and VEKOP-2-3-2-16-2017-00014 was supported by the European Union and the State of Hungary, co-financed by the European Regional Development Fund.

Laboratory News

  • ACWF: Database and analysis sofware for amyyloid fibril structures

    We introduce a new computational tool (ACWF, Amyloid Coordinate Wizard Fibril) developed for analysis and visualization of 3D structures of amyloid fibrils. The presented hierarchical clustering method enables the classification of polymorphs into larger structural families and the identification of disease-specific structural differences. Beta-sheets segmented by arc motifs form the amyloid architecture - in these structures steric zippers ensure solvent exclusion. These complementary molecular surfaces were characterized by local values of three parameters, steric fit, area and interdigitation. Using these parameters, the amino acid residues forming structural hotspots were identified, displaying distinct patterns in each structural family. This framework provides a better understanding of how molecular-level interactions evolve into complex pathological formations, and how the zipper region changes locally as more compact structures emerge during the maturation of amyloids.
    We publisher these results in the Journal of Chemical Information and Modeling. The database and wizard is available as a plugin for PyMol program, here (link).

  • Intramolecular Inhibition by Imidazole in Acid-Catalyzed Hydrolysis of Protected Carbohydrates

    The study uncovers an anomaly in the acid-catalyzed hydrolysis of the 5,6-O-isopropylidene group in specific D-gluco- and D-allofuranose derivatives, linked to C3-epimers with 3-O-imidazole sulfonyl moieties. Advanced modeling reveals how interactions between protecting groups and steric effects inhibit this reaction, providing new insights into carbohydrate chemistry.

    Kép1

  • ACW: Database and toolkit for analyzing the zipper regions of amyloid oligopeptide structures

    Amyloidogenic proteins contain short segments (amyloid prone regions) that nucleate formation of large sandwiched β-sheet structures. Analysis of structural properties of interfaces formed between the interacting β-sheets of these oligopeptides is essential for understanding their amyloidogenicity and self-assembly. We developed a tool (ACW plugin for the PyMOL program) for visualization and comparative analysis of amyloid oligopeptide crystal structures and applied it to the database of amyloid oligopeptides derived from the PDB. Our data show that parallel β-sheet structures have higher entanglement and better shape complementarity, probably related to their higher abundance. Our paper was published in the Journal of Chemical Information and Modeling.

    Acw Highlights Fig

  • ELTE-CrystalLAB: Interactive program at the Hungarian "Researcher’s Night” event

    We participated in the Hungarian popular science event "Researcher’s Night" with a hands on demo lab entitled "Tales about crystals". (In Hungarian). 

    Mirol Meselnek A Kristalyok Fig

  • Amyloidogenic hexapeptides

    In our latest article we studied amyloidogenic hexapeptides in solution and crystalline phases. We have shown that small modifications of the experimental conditions can result in extraordinarily diverse amyloid structures. These results indicate that amyloid polymorphism, which plays impotant role in the biologly of amyloids, can be modelled effectively with short peptides.

  • Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation

    A group of hormone peptides is stored in the form of functional amyloid fibers in acid secretion vesicles before they reassemble their biologically active helical spatial structure when they enter the blood circulation. In the article published in Nature Communications, we explain the molecular basis of pH-dependent reversible amyloid formation in the case of gastrointestinal peptides belonging to the glucagon family. The article is presented on the website of the MTA by several Hungarian online newspapers. [1, 2, 3]

  • High affinity binding in a flexible protein-protein complex: structural studies on the calmodulin – melittin complex

    Interaction of calmodulin and melittin is widely used as a test system for method development, and as a reference in studies of calmodulin interactions. However, results on the interaction pattern of this complex were non-conclusive so far. Our aim was to explore the fine details of this interaction. Our crystallographic study revealed multiple different binding modes, and our succeeding MD simulations concluded that these could transform to each other: the nanomolar affinity binding of this complex is realized by a ‘slippery’ binding way and interchanging interactions.
    Our publication has been selected as one of "Editors' Picks," of the Journal of Biological Chemistry.

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