AG Krey

Research summary

Our research is focused on structural studies in order to understand molecular mechanisms that are essential for various steps of the virus cycle.

Our major goals are:

  1. Structural characterization of virus glycoproteins involved in membrane fusion and interactions with the immune system and identification of the determinants of an efficient neutralizing antibody response to facilitate informed vaccine design. During the last years we have contributed the structures of a number of neutralizing epitopes recognized by neutralizing antibodies within the major glycoprotein E2 of the hepatitis C virus (HCV). Based on these structures we concluded that the binding site for the cellular receptor CD81 - representing the major target of neutralizing antibodies - is conformationally flexible. This conformational flexibility likely constitutes a novel strategy that HCV utilizes to evade potently neutralizing antibodies.
  2. The recent structural characterization of the C. elegans cell fusion protein EFF-1 revealed that certain effector proteins driving virus-cell fusion and cell-cell fusion are structurally homologous and also share mechanistic similarities. We are currently evaluating, whether - in addition to the structural homology of the effector proteins - both processes also share other common features or key players.
  3. More recently we also started to investigate the mechanism-of-action leading to the assembly and disassembly of large viral capsids, an essential step for the production of virus progeny as well as for the release of the viral genome during virus entry.

We study mostly viruses that constitute a global public health and/or veterinary concern and use structural biology/biophysical methods with a special focus on X-ray crystallography. The structural knowledge gained from our experiments can be used for structure-based design of preventive or curative antiviral agents, i.e., this knowledge has a direct potential for translational medicine. Furthermore, structural studies are often performed in parallel on homologous proteins from related viruses, which provides crucial information about the evolutionary relationship between these viruses and allows the identification of conserved features and/or pathways, which often are the most promising drug targets.


Structures

Prof. T. Krey/MHH

View on the paratope of the neutralizing anti-HCV E2 Fab fragment 3/11 in complex with an epitope peptide (Meola et al., 2014).

Prof. T. Krey/MHH

View on the paratope of the neutralizing anti-HCV E2 Fab fragment HC84-27 in complex with an epitope peptide (Krey et al., 2013).

Prof. T. Krey/MHH

Ribbon diagram of a trimer of the C. elegans cell fusion protein EFF-1 next to the trimer of the tick-borne encephalitis virus (TBEV) glycoprotein E (Perez-Vargas, Krey et al., 2014).

Prof. T. Krey/MHH

Electrostatic surface potential of the BVDV glycoprotein Erns harboring the active site of the RNase (Krey et al., 2012).

Group members

Prof. T. Krey/MHH
Prof. Dr. Thomas Krey

Team leader

  • Prof. Dr. Thomas Krey

Medizinische Hochschule Hannover (Hannover Medical School)
Institute of Virology, OE5230
Carl-Neuberg-Str. 1
30625 Hannover

Phone +49 511 532 4307 (Heike Böning, TA)
Departmental Secretary +49 511 532 6736
Laboratory +49 511 532 4314 / 4315 | FAX +49 511 532 8736
Email Krey.Thomas@MH-Hannover.de


AG Krey/MHH
AG Krey/MHH

Funding

Current funding

"RESIST" Cluster of Excellence, Resolving Infection Susceptibility

Projects: B10, D1, D3

go to website
DFG - "CRC 900"

Collaborative Research Centre, Project B10
Chronic infections: microbial persistence and its control

go to website

Publications in peer-reviewed journals, Reviews, Book chapters, Comments etc.

Selected Publications: