Structure of key protein complex uncovered
Researchers at Memorial Sloan-Kettering Cancer Centre (MSKCC) in the USA have uncovered the structure of a network of proteins that help regulate the life cycle of cells. Understanding the network's physical layout is an important step toward learning its function, and in finding ways to correct flaws in the system that could lead to cancer.
The researchers were able to identify the way in which the molecules " called the Small Ubiquitin-related Modifiers (SUMO-1) " within the protein complex were connected or "conjugated' to one another. The findings offered the first complete look at the structure of these molecules since they were thought to exist in the cell.
"Understanding this process could be important in many physiological steps that are disrupted in cancer," said Christopher Lima, PhD, a structural biologist at the Sloan-Kettering Institute and lead author of the study.
Dr Lima noted that yeast cells that lack SUMO cannot successfully divide, and since cancer is characterised by cells dividing unchecked, proving SUMO's function could potentially yield novel anticancer therapies.
SUMO has been considered a "mysterious cousin" of ubiquitin " a protein acts as a chemical tattoo that tags and regulates damaged or obsolete many cell-cycle proteins for destruction. Cancer researchers have become particularly interested in ubiquitin since its special property has been discovered.
Dr Nikola Pavletich, chairman of the structural biology program at the Sloan-Kettering Institute, and an expert in ubiquitin, said the latest work had provided a new view and a detailed understanding of the process of sumoylation and should lead to a better grasp of SUMO and ubiquitin.
"Identifying the additional roles of sumoylation may well provide us with new targets to inhibit the protein and therapeutic agents for cancer and other conditions in which SUMO is involved," Dr Pavletich said.
Dr Lima and his colleagues proposed that the next step in the research would be to probe the importance of the contacts observed in the discovered structure with the biochemical activities and effects on the cell itself of disrupting these contacts.
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