Structure and mechanism of the human mitochondrial ADP/ATP carrier


   Mitochondrial Biology Unit

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  Prof E Kunji  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The mitochondrial ADP/ATP carrier, also called the adenine nucleotide translocase, imports ADP into the mitochondrial matrix and exports ATP, which are key steps in oxidative phosphorylation. The structures of the cytoplasmic-open and matrix-open states have been resolved (1, 2), but it is unknown how substrate binding leads to conformational changes of the carrier.

This project will be carried out in the group of Prof. Kunji, which studies transport processes in mitochondria, in particular those involving members of the mitochondrial carrier family SLC25 (2, 3).

This aim of this project is to solve the structure of the mitochondrial ADP/ATP carrier in different states to understand the molecular basis of substrate interactions with the carrier. Its substrate specificity and mechanistic properties will be analysed by using bioinformatic, biophysical and biochemical methods and transport assays using robotics. Once transport states have been defined, nanobodies, which are camelid antibodies, will be selected and the structures of the different states will be solved by x-ray crystallography or single particle analysis of cryo-EM images. Thus, the candidate will be in the position to apply a wide range of different techniques to discover the fundamentals of this important transport protein.

Keywords

General: mitochondria, mitochondrial ADP/ATP carrier, adenine nucleotide translocase, transport processes, oxidative phosphorylation

Research Group: https://www.mrc-mbu.cam.ac.uk/research-groups/kunji-group

Biological Sciences (4) Medicine (26)

Funding Notes

Details about funding and eligibility are available on our website: https://www.mrc-mbu.cam.ac.uk/postgraduate-studies
The start date: October 2024.
Applications will not be accepted via the enquiry email address. This address is to ask the supervisors for further information about the project. For details on how to apply please see our postgraduate studies webpage: https://www.mrc-mbu.cam.ac.uk/postgraduate-studies.

References

1. Ruprecht, J.J., Hellawell, A.M., Harding, M., Crichton, P.G., McCoy, A.J. & Kunji, E.R. Structures of yeast mitochondrial ADP/ATP carriers support a domain-based
alternating-access transport mechanism. Proc Natl Acad Sci U S A 111, E426-434 (2014). doi:10.1073/pnas.1320692111
2. Ruprecht, J.J. et al. The molecular mechanism of transport by the mitochondrial ADP/ATP carrier. Cell 176, 435–447 (2019). doi:10.1016/j.cell.2018.11.025
3. Ruprecht, J.J. & Kunji, E.R.S. Structural Mechanism of Transport of Mitochondrial Carriers. Annu Rev Biochem 90, 535-558 (2021). doi:10.1146/annurev-biochem-
072820-020508
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