www.ciisb.org  |  15 Sep 2022, 9:10

Newsletter

Editorial

Dear Colleagues,

as of August 22, 2022, the new two-year term of the renewed CIISB Executive Committee (EC) started. Congratulations to the structural virologist Pavel Plevka, who has been appointed as the new Chair of the Czech Infrastructure for Integrative Structural Biology (CIISB). I have had an honor to chair this Executive Committee since 2010. In the period 2011-2015, ten core facilities were built at BIOCEV and CEITEC and the CIISB modus operandi was established, including arrangements for internal, external, and transnational access.

Currently, CIISB represents one of 11 national research centers of the large pan-European research infrastructure in structural biology Instruct-ERIC. CIISB is equipped with state-of-the-art technologies and serves wide national and international scientific community. Thanks to the generous support of the Ministry of Education, Youth and Sports and their programs supporting investment and operations of large research infrastructures in 2016-2022, CIISB maintains a privileged position in the field of integrated structural biology at European and global level and contributes to more than a hundred cutting-edge scientific papers published in prestigious international journals every year. At the end of my tenure, I would like to express my sincere thanks to all colleagues who were essential and made the success of CIISB possible: to all members of the EC and of the International Advisory Board, to core facility heads and their teams, to administrative staff, who took excellent care of all grants and financial resources, and last but not least also to the leaderships of both the Institute of Biotechnology, Czech Academy of Sciences, and CEITEC Masaryk university, and their mother institutions BIOCEV and CEITEC, for their support and encouragements. And I must not forget to also thank our users who make extensive use of the CIISB services and instrumentation and for whom the CIIB services are primarily intended. I wish the new Chair and the entire Executive Committee wise decisions and much patience and diligence in securing funding for CIISB's operations and investments in the upcoming, financially very uncertain period 2022-2029.

Vladimír Sklenář

Dear Colleagues,

Foremost, I would like to thank Vladimír Sklenář for his 12 years of service as the Chair of the Czech Infrastructure for Integrative Structural Biology (CIISB) Executive Committee (EC). Vladimír had a pivotal role in conceiving the idea of CIISB, gaining the initial funding, and establishing CIISB as an efficient infrastructure that supports scientists in performing excellent research. It is particularly noteworthy because prior to CIISB's establishment, there was a limited tradition of shared infrastructures in structural biology in the Czech Republic. Vladimír's distinguished guidance was essential for integrating CIISB infrastructures into Europe-wide networks of Instruct and Instruct-ERIC.

Over the years, CIISB became the backbone of the Czech structural biology community and enabled both Czech and international scientists to measure data using state-of-the-art instruments and thus gain insight into fundamental biological processes. Scientists working at CIISB facilities contribute their unique expertise in data measurements and analysis to researchers that are new to the structural biology field and thus lower the, often substantial, entry barrier facing those who want to understand the mechanisms of function of biological macromolecules. Vladimír and other members of EC demonstrated courage and prescience in promoting CIISB laboratories to adopt novel technologies, such as cryo-electron microscopy, in their early days, which enabled Czech researchers to stay at the forefront of scientific discoveries.

I look forward to working with our colleagues from BIOCEV and CEITEC, and to the challenge of supporting CIISB in its mission of providing prime services and expertise in the field of structural biology. I would like to acknowledge the continued support from the Research, Development, and Innovation Council and the Ministry of Education, Youth, and Sports.

September 12, 2022

Pavel Plevka

Pavel Plevka became the new chairman of the Czech Infrastructure for Integrative Structural Biology CIISB

Structural virologist Pavel Plevka has been appointed as the new Chairman of the Czech Infrastructure for Integrative Structural Biology (CIISB). He succeeds structural biologist Vladimir Sklenar, who has been advocating, together with Jaroslav Koca, for establishing shared infrastructures since 2010, following the example of Western European countries.

Professor Ray Freeman, one of the pioneers and giants of nuclear magnetic resonance, passed away.

We are greatly saddened to hear that Professor Ray Freeman (FRS), the former John Humphrey Plummer Professor of Magnetic Resonance, Fellow of this College from 1987 and Emeritus Fellow from 1999, died on May 1, 2022 aged 90 and we offer his family our deep condolences.

New imaging system Li-COR Odyssey M available at CF BIC

The instrument fills the role of a Western blot imager, plate reader, slide scanner, fluorescence (488, 520, 685 and 785 nm) and luminescence imager. It is compatible with membranes, gels, plates and microscopy slides.

Microscale Thermophoresis technique workshop at BIOCEV

On October 4-5, CMS with experts from NanoTemper company are organizing a workshop on the characterization of biomolecular interaction by the Microscale Thermophoresis technique and protein stability with particle size determination by Prometheus Panta.

24th Heart of Europe Bio-Crystallography Meeting

The Heart of Europe Bio-Crystallography Meeting (short HEC-Meeting) is an annual academic conference on structural biology, in particular protein crystallography. Researchers from universities, other research institutions and industry from Austria, Czech Republic, Germany and Poland meet to present and discuss current topics of their research. The conference will be held on 22-24 September 2022.

30th Protein Structure Determination in Industry meeting

On behalf of PSDI and its Executive Committee, it is our pleasure to invite you to the 30th Protein Structure Determination in Industry meeting, which will be held at the Van der Valk Hotel, Eindhoven, in The Netherlands from Sunday 23rd to Tuesday 25th October 2022.

 

CIISB Access

Applications January - July

  • 92 internal applications
  • 47 external applications
  • 20 applications from foreign users

You can find more information here.

Applications overview in total

  Internal users External users Foreign users
2016 123 35 5
2017 178 50 14
2018 177 51 15
2019 147 58 27
2020 183 94 13
2021 166 69 16
2022 92 47 20

Save the date

Bio-SAXS practical course 2022

13 – 14 September 2022

The Centre of Molecular Structure of CIISB is organizing the BioSAXS Practical Course 2022, which will be held in BIOCEV on 13th and 14th September 2022.

Microscale Thermophoresis technique workshop at BIOCEV

4 – 5 October 2022, 10:00 AM – 6:00 PM

Workshop on the characterization of biomolecular interaction by the Microscale Thermophoresis technique and protein stability with particle size determination by Prometheus Panta.

ARIA meeting for Instruct facility personnel

3 November 2022

Meeting will cover issues related to managing access through ARIA.

Research Highlights

EMBO J. 2022

Cryo-EM structures of CspA27 inside the exit tunnel

A. Structure and nascent chain contacts in the exit tunnel for CspA27-1.
B. Structure and nascent chain contacts in the exit tunnel for CspA27-2.
C. Structure and nascent chain contacts in the exit tunnel for CspA27-3.

Marina V. Rodnina Research Group

Significance

Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of a β-barrel protein begins with formation of a dynamic α-helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N-terminal part of the nascent chain refolds to a β-hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α-helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl-transferase center suggest that protein folding could modulate ribosome activity.

Agirrezabala, X.; Samatova, E.; Macher, M.; Liutkute, M.; Maiti, M.; Gil-Carton, D.; Novacek, J.; Valle. M. & Rodnina, M. V.: EMBO J. (2022) e109175, https://doi.org/10.15252/embj.2021109175

Science Advances 2022

Overview of hcis-PT structure and reaction scheme

(A) Cartoon representation of a single DHDDS-NgBR heterodimer in complex with FPP [Protein Data Bank (PDB) 6Z1N]. DHDDS and NgBR are colored blue and yellow, respectively. Surface representations of the FPP and IPP [placed by superposition with PDB 6W2L] molecules are colored pink and green, respectively. The residue W3, at the DHDDS N terminus, is shown as spheres.

(B) Condensation reaction scheme. At the first cycle, the allylic diphosphate primer, FPP (C15, pink), undergoes a condensation with IPP (C5, green) to produce geranylgeranyl-diphosphate (GGPP) (C20). The cycle repeats with further condensations (14–17) of the allylic diphosphate at S1, ultimately leading to a final product length of C85–100.

Yoni Haitin Research Group

Significance

Isoprenoids are synthesized by the prenyltransferase superfamily, which is subdivided according to the product stereoisomerism and length. In short- and medium-chain isoprenoids, product length correlates with active site volume. However, enzymes synthesizing long-chain products and rubber synthases fail to conform to this paradigm, because of an unexpectedly small active site. Here, we focused on the human cis-prenyltransferase complex (hcis-PT), residing at the endoplasmic reticulum membrane and playing a crucial role in protein glycosylation. Crystallographic investigation of hcis-PT along the reaction cycle revealed an outlet for the elongating product. Hydrogen-deuterium exchange mass spectrometry analysis showed that the hydrophobic active site core is flanked by dynamic regions consistent with separate inlet and outlet orifices. Last, using a fluorescence substrate analog, we show that product elongation and membrane association are closely correlated. Together, our results support direct membrane insertion of the elongating isoprenoid during catalysis, uncoupling active site volume from product length.

Giladi, M., Bar-El, ML., Lisnyansky, M., Vankova, P., Ferofontov, A., Melvin, E., Alkaderi, S., Kavan, D., Redko, B., Haimov, E., Wiener, R., Man, P., and Haitin, Y.: Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases, Sci. Adv. 2022, 7, eabn1171, https://doi.10.1126/sciadv.abn1171

Research Highlights Archive

Selected publications

L. Fojtik, et al.: Fast Fluoroalkylation of Proteins Uncovers the Structure and Dynamics of Biological Macromolecules, Journal of the American Chemical Society, 143 (2021) 20670-20679, 10.1021/jacs.1c07771

M. Koktava, et al.: Metal Oxide Laser Ionization Mass Spectrometry Imaging of Fatty Acids and Their Double Bond Positional Isomers, Anal. Chem., 94 (2022) 8928-8936, 10.1021/acs.analchem.2c00551

X. Agirrezabala, et al.: A switch from alpha-helical to beta-strand conformation during co-translational protein folding, Embo J., 13 (2022), 10.15252/embj.2021109175

M. Giladi, et al.: Structural basis for long-chain isoprenoid synthesis by cis-prenyltransferases, Sci. Adv., 8 (2022) 14, 10.1126/sciadv.abn1171

P.R. Tharra, et al.: Short Synthesis of (+)-Actinobolin: Simple Entry to Complex Small-Molecule Inhibitors of Protein Synthesis, Angewandte Chemie-International Edition, (2022) 7, 10.1002/anie.202116520

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