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Highlights of our Work
BAR domain

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Olga Svinarski and VMD

The cells of higher life forms, so-called eukaryotic cells, are subdivided through many internal membranes made of lipid bilayers. The internal membranes assume numerous shapes, like spheres, tubes or parallel sheets. Outside of cells, biological membranes adopt usually flat shapes and the question arises, how do eukaryotic cells sculpt their inner membranes? The question of flat membrane sculpting is particularly interesting also as mature cells constantly produce new membrane shapes, for example spherical vesicles filled with certain biomolecules destined for release into the extracellular space, a process called exocytosis. The cell has many mechanisms available for sculpting its membranes, one of them relying on proteins called BAR domains that act from the surface of lipid bilayers. Molecular modeling with NAMD and VMD has provided valuable views of BAR domains at work in case of the so-called N-BAR family (see the earlier highlights Protein Teamwork, Jun 2009 and Proteins Sculpting Cell Interior, Sep 2008). Researchers report now an extension of the earlier studies to the F-BAR domain family of membrane sculpting proteins. The new modeling work is particularly exciting as it can be directly compared to electron microscopy images of membrane tubes sculpted from flat membranes in experiments done outside of cells. The new studies reveal how F-BAR domains sculpt tubular membranes through the shape of dimerized domains and through F-BAR domains not acting individually, but as an army of F-BAR domains adopting an ordered formation on one side of the membrane. More on our F-BAR domain web page.
Highlights of our Work
PI4K

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see also movie
made with VMD

The Golgi apparatus found in so-called eukaryotic cells acts like Amazon.com, namely accepting delivery of newly synthesized proteins, packaging them, and sending them out. However, in comparison to Amazon.com the Golgi apparatus uses immensely more advanced packaging materials made of a multitude of lipids. The various lipids form membranes in the shape of vesicles. Depending on lipid type specific goods are packaged inside the vesicles, specific locations in the cell receive the packages, content is emptied there and packages are retrieved. To achieve the series of steps just outlined, lipids as the main actors need to be coordinated. One way is to recognize lipids forming vesicle membranes and to modify them to be readied for a subsequent step, for example going from release step to retrieval step. For this purpose eukaryotic cells engage a special class of proteins, named kinases, that can recognize membrane lipids and phosphorylate them, adding a so-called phosphate group. As reported recently, a team of experimental and computational scientists determined the atomic structure of a key member in the kinase family, phosphatidylinositol 4-kinase (PI4K). The scientists discovered not only the structure, but also how PI4K captures and phosphorylates a particular type of lipid molecule, thereby changing a vesicular membrane and turning on the next step in the cellular package delivery system. The discoveries, made possible through the software NAMD and VMD, are expected to have an impact on the design of novel drugs that suppress cancer cell growth. More on our kinase website.

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