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Medicine

How a fungus helped scientists see into the heart of cell membranes

A new study uses a toxin to stabilize the interaction between two key lipids, revealing secrets about how cholesterol is organized in cellular membranes.

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1 min read

In the intricate world of cell membranes, where hundreds of lipid species come together to form a complex two-dimensional liquid, one interaction stands out for its crucial role in maintaining cellular health. The bond between sphingomyelin and cholesterol is like a delicate dance, providing vital protection against microbial invasion, restraining excessive cell growth, and keeping cellular lipids in balance. Yet, the structure of this intricate partnership had remained elusive, much like trying to grasp a fleeting shadow.

Enter Ostreolysin A, a fungal toxin that binds to sphingomyelin-cholesterol complexes with remarkable specificity. By harnessing OlyA's unique properties, researchers were able to stabilize the SM/cholesterol interaction in a way that antibodies do for protein complexes. This breakthrough allowed them to study the importance of hydrogen bonding in holding this critical partnership together.

As we peer into the heart of the lipid bilayer membrane, we find a complex web of interactions that underpin cellular function. The story of OlyA and its role in stabilizing the SM/cholesterol interaction is one of scientific ingenuity and discovery. What matters here is not just the technical breakthrough, but the fundamental understanding it brings to our comprehension of cell membranes – a crucial frontier in the ongoing quest to unravel the mysteries of life itself.

The people behind the work

  • Smothers JC et al.

    Author

    Published in Proceedings of the National Academy of Sciences of the United States of America

Source: Proceedings of the National Academy of Sciences of the United States of America

Sources & Verification

Every statement in this story is drawn from the facts below. Each is linked to a primary or reputable source — follow any citation to check it for yourself.

  1. Biomembranes are complex two-dimensional liquids composed of hundreds of lipid species that interact in a myriad of ways. Proceedings of the National Academy of Sciences of the United States of America
  2. One such interaction, that between sphingomyelin (SM) and cholesterol in plasma membranes of animal cells, provides many functional benefits, including protection from microbial infection, prevention of unrestrained cell growth, and proper maintenance of cellular lipid composition. Proceedings of the National Academy of Sciences of the United States of America
  3. Owing to the liquid nature of membranes, the structure of the SM/cholesterol interaction, or any other functionally critical lipid-lipid interaction, has remained elusive. Proceedings of the National Academy of Sciences of the United States of America
  4. Here, we overcome this challenge using a fungal toxin called Ostreolysin A (OlyA), that has been shown to specifically bind to SM/cholesterol complexes in membranes. Proceedings of the National Academy of Sciences of the United States of America
  5. We used OlyA to stabilize the SM/cholesterol interaction much in the same way as antibodies are used to stabilize preexisting protein complexes. Proceedings of the National Academy of Sciences of the United States of America
  6. The importance of hydrogen bonding in stabilizing the SM/cholesterol interaction is supported by structural analysis of a mutant form of OlyA that binds free SM in a cholesterol-independent manner. Proceedings of the National Academy of Sciences of the United States of America
  7. These results provide structural insights into the organization of cholesterol in membranes. Proceedings of the National Academy of Sciences of the United States of America

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