A molecular machine, which plays an essential ‘cargo’ role in controlling the delivery of proteins to the surface of human cells has been identified using artificial intelligence (AI).
The research has shown how manipulating this process could treat or prevent disease, with implications for SARS-CoV-2, human papillomavirus (HPV) and Alzheimer’s disease.
The study was conducted by researchers at the Universities of Bristol (UK) and Queensland (Australia), and the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK.
They sought to understand how Commander, a molecular machine composed of sixteen individual proteins, is assembled and how mutations in its function play a role in Ritscher-Schinzel syndrome, a rare disease characterised by intellectual disability and development delay.
Professor Pete Cullen, one of the study’s lead authors from the School of Biochemistry at the University of Bristol, explained: “The surface of every human cell is studded with an array of proteins through which they engage with their neighbours and sense their environment. How these proteins reach the cell surface in the right amount and at the right time is fundamental to understanding human development and the process of healthy human ageing.”
Role in various diseases
By combining biochemical and cell-based experiments with artificial intelligence, the researchers were able to precisely define how individual parts of Commander come together to form the functional machine and how this acts as one of the cell’s ‘postal workers’.
Knowing the structure of the Commander complex has allowed the researchers to better understand how disease-causing mutations provoke Commander to malfunction in Ritscher-Schinzel syndrome and advance our understanding of how it is involved in other diseases.
Viruses such as SARS-CoV-2 and HPV need the Commander complex to infect cells. Commander has also been linked to the transport of the amyloid protein in Alzheimer’s disease.
Professor Cullen said: “Excitingly, we now have a blueprint for thinking of ways that we can manipulate Commander function to help with these and other diseases associated with defects in the fascinating molecular machine.”
