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Proteins in Motion

Proteins are essential components of living organisms with multiple tasks and diverse mechanisms. The scientists at the CSS have set themselves the goal of elucidating and understanding these mechanisms.

By combining different techniques (MX, SAXS, molecular modeling) we are able to investigate the function of proteins in the CSS. Proteins change their spatial arrangement (conformation) or form a complex together with other proteins to perform their function. With our methods we can analyze and visualize individual conformational changes, substrate binding and also complex formation and thus contribute to the understanding of mechanisms of proteins and their action partners.

We have visualized here the movement of two different proteins to illustrate our work. The video "EctA in motion" shows a partial step of the synthesis of a natural product and "Pdr5 in motion" shows the transport mechanism of an efflux pump.

EctA in motion

Ectoine is a chemical chaperone and has extensive applications in cosmetics, medicine and biochemistry, but the mechanism of ectoine biosynthesis has not yet been fully elucidated. In 2020, CSS was able to help elucidating the second step of ectoine biosynthesis, catalyzed by L-2,4-diaminobutyrate acetyltransferase (EctA). In the video, one can see how first EctA (blue) changes its conformation to bind acetyl-CoA (red). After another conformational change, the substrate L-2,4-diaminobutyrate (DAB, orange) can then be bound and the acetyl group is transferred to the substrate, forming N-γ-acetyl-L-2,4-diaminobutyrate (N-γ-ADABA, green).

Our findings provide detailed insights into the function of the enzyme and the formation of the ectoine precursor. This information can be used to improve the biotechnological production of this valuable chemical chaperone.

A.A. Richter et al. (2020), doi: 10.1074/jbc.RA119.011277

Pdr5 in motion

Not only antibiotic resistance develops but also protective mechanisms against antifungal compounds. An example of this is the ABC transporter Pdr5, which is capable of transporting a wide range of chemicals and is thus involved in multiple drug resistance. In the video it can be seen how the entire transporter with nucleotide binding domain (NBD, yellow), transmembrane domain (TMD, blue) and extracellular domain (ECD, pink) undergoes a conformational change. The transport channel is initially open inward to the cytoplasmic side (inward-facing). A peristaltic movement of the transporter allows the substrate to be transported through the amphipathic channel to the outside, the extracellular side (outward-facing). The cross-section of the solvent-excluded surface is shown in gray.

This video explains the multiple resistance effect of Pdr5 and lays a foundation for the development of new antifungal agents.

A. Harris et al. (2021), doi: 10.1038/s41467-021-25574-8.

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