Author response: Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex
Year: 2014
Type: peer-review
Abstract: To survive starvation and other hard times, cells have developed a unique recycling strategy: they can scavenge the resources they need from within the cell itself. To do this, the cell forms a double-layered envelope around particular sections of the cell to seal them off from the rest. Then, the contents of the envelope are taken apart and the resulting raw materials are sent elsewhere in the cell where they can be used as required. This process is called autophagy. In more complex organisms like humans, autophagy can have additional roles. One of the key proteins involved in autophagy—called BECN1—suppresses the growth of tumors, and the gene that makes BECN1 is missing in 40–70% of human breast, ovarian, and prostate cancers. Autophagy may also help to prevent Huntington's disease and other similar conditions by stopping disease-causing proteins or broken cell parts from building up inside brain cells. The BECN1 protein does not work alone. Instead, it becomes part of a group, or ‘complex’, of several proteins that are required to form the envelope made during autophagy. However, the three-dimensional structure of the protein complex is unclear. Baskaran et al. used electron microscopy and other techniques to investigate this structure and found that the complex forms a V shape with two arms, which is held together by its largest protein, VPS15. This protein also acts as a bridge between BECN1 and another protein that is a target for new cancer drugs, called VPS34. Next, Baskaran et al. used a different set of techniques to determine how the complex moves. This revealed that many of the connections between proteins in the complex are flexible. However, one of the arms is inflexible and this limits the ability of the VPS34 protein to move. Understanding this structural constraint may help us to design drugs that are able to target the protein complex more efficiently.
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2989211368