26. September 2024

Central mechanism of inflammation decoded Central mechanism of inflammation decoded

Bonn researchers use nanobodies to elucidate pore formation by gasdermin D in cell membranes

Bonn researchers use nanobodies to elucidate pore formation by gasdermin D in cell membranes
The formation of pores by a particular protein, gasdermin D, plays a key role in inflammatory reactions. During its activation, an inhibitory part is split off. More than 30 of the remaining protein fragments then combine to form large pores in the cell membrane, which allow the release of inflammatory messengers. As methods for studying these processes in living cells have so far been inadequate, the sequence of oligomerization, pore formation and membrane incorporation has remained unclear. An international research team led by the University Hospital Bonn (UKB) and the University of Bonn has succeeded in answering this question with the help of antibody fragments, so-called nanobodies, which they have identified. They hope that this will lead to potential therapeutic applications. Their results have now been published in the journal “Nature Communications”. 

Central mechanism in inflammation decoded
Central mechanism in inflammation decoded - Prof. Florian I. Schmidt and Lisa Schiffelers use nanobodies to clarify the formation of pores by gasdermin D in cell membranes © Rolf Müller, UKB
Download all images in original size The impression in connection with the service is free, while the image specified author is mentioned.
Please fill out this field using the example format provided in the placeholder.
The phone number will be handled in accordance with GDPR.

Inflammasomes, large multiprotein complexes of the innate immune system, activate and control inflammatory reactions in our body. An important step of the signaling cascade triggered by them is the cleavage of the protein gasdermin D (GSDMD). The active part of GSDMD, the so-called N-terminal domain (NTD), can then form pores in cellular membranes, which on the one hand enable the release of pro-inflammatory cytokines and on the other hand trigger pyroptosis – a form of cell death that further fuels inflammation. “But how exactly and where GSDMD assembles into pores, and whether this step can be inhibited, was previously unclear,” says Prof. Florian I. Schmidt from the Institute of Innate Immunity at UKB, who is a member of the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Area (TRA) “Life & Health” at the University of Bonn.

To clarify these open questions, Prof. Schmidt’s research team used protein inhibitors that they derived from particular antibodies found in alpacas. These so-called nanobodies are around ten times smaller than normal antibodies. By binding to proteins, they can disrupt their function or mark certain molecules and thus make them visible. The Bonn researchers identified six nanobodies against GSDMD. In their study, they introduced the genetic information of two representatives into […]

Read More 

 

The authors acknowledge the support from the Flow Cytometry Core Facility.

Lisa D.J. Schiffelers et al: Antagonistic nanobodies implicate mechanism of GSDMD pore formation and potential therapeutic application, DOI: https://doi.org/10.1038/s41467-024-52110-1

Dr. Florian I. Schmidt
Institute for Innate Immunity
University Hospital Bonn,
ImmunoSensation &2 (TRA) "Life & Health", University of Bonn
Office: +49-228/287-51124
E-mail: fschmidt@uni-bonn.de

Wird geladen