Structural mechanism of the E. coli drug efflux pump AcrB

In a new study published online in the open access journal PLoS Biology, Gaby Sennhauser, Marcus Gruetter, and colleagues use structural biology techniques to probe the molecular mechanisms of the major drug efflux pump in E. coli AcrB.

Bacterial resistance to antibiotics is a major challenge for the current treatment of infectious diseases. One way bacteria can escape destruction is by pumping out administered drugs through specific transporter proteins that span the cell membrane, such as AcrB.

Making use of designer proteins that bind to and stabilize proteins of interest, the researchers were able to obtain better resolution structural data for the AcrB complex. After selecting for designed ankyrin repeat proteins (DARPins) that inhibit this pump, Sennhauser and colleagues solved the crystal structure of the DARPin inhibitor in complex with AcrB. They were able to confirm that the AcrB pump is split into three subunits, each of which exhibit distinctly different conformations.

Each subunit has a differently shaped substrate transport channel; these variable channels provide unique snapshots of the different phases employed by AcrB during transport of a substrate. The structure also offers an explanation for how substrate export is structurally coupled to simultaneous proton import--thus significantly improving our understanding of the mechanism of AcrB. This is the first report of the selection and co-crystallization of a DARPin with a membrane protein, which demonstrates not only DARPins' potential as inhibitors, but also as tools for the structural investigation of integral membrane proteins.


Contact: Natalie Bouaravong
Public Library of Science

Page: 1

Related biology news :

1. Structural basis for photoswitching in fluorescent proteins brought into focus
2. Weizmann Institute scientists discover a control mechanism for metastasis
3. New mechanism links smoking to lung damage
4. Identified mechanism in the malaria parasite to help it adapt to infected individuals
5. Identifying the mechanism behind a genetic susceptibility to type 2 diabetes
6. A new plant-bacterial symbiotic mechanism promising
7. MIT IDs mechanism behind fear
8. Tracing Parkinsons lethal mechanism
9. Researchers shed light on mechanism of action used by anti-cancer drug
10. A new plant-bacterial symbiotic mechanism promising for crop applications
11. Simulations unravel outer membrane transport mechanism

Post Your Comments:

(Date:8/26/2020)... and SHANGHAI (PRWEB) , ... August 24, 2020 ... ... novel approaches for the treatment of chronic inflammatory and fibrotic diseases, today announced ... and Vice President of Drug Discovery. , Dr. Canan previously served as Executive ...
(Date:8/26/2020)... ... August 25, 2020 , ... ... solutions for drugs, biologics, cell and gene therapies, and consumer health products, today ... PEGS Boston Virtual Conference & Expo, taking place between Aug. 31 – September ...
(Date:8/23/2020)... ... August 21, 2020 , ... ... has been published and is now available on the company’s global website. Crystallography ... X-ray analysis community, presenting current news and crystallographic research. , The latest ...
Breaking Biology News(10 mins):
(Date:7/18/2020)... (PRWEB) , ... July 16, 2020 , ... After research ... The completion of a great surgery is only the beginning of a successful study, ... research community. , Join Brad Gien, Global Head of Surgery from Envigo ...
(Date:7/18/2020)... ... 2020 , ... Medial EarlySign , a leader in ... high-burden diseases, and Centric Consulting, a business and technology consulting firm, today announced ... in order to identify and prioritize patients for care. , Combining Centric’s management ...
(Date:7/10/2020)... LORTON, Va. (PRWEB) , ... July 08, 2020 ... ... laboratory testing services and products, announces a significant expansion of laboratory operations through ... robust collection for agencies implementing testing programs. , Bode-CARES provides ...
(Date:7/10/2020)... ... July 09, 2020 , ... ... is commonly used to suppress pigment formation in zebrafish embryos, maintaining optical transparency ... led by Dr MA has been using the zebrafish model to investigate the ...
Breaking Biology Technology:
Cached News: