Model systems for complex protein-interplay
Viruses and bacteria are able to couple to cells by small recognition points at cell membranes. The virus establishes to all of these recognition points a connection: the origination of cooperation. This complex interplay is sometimes completely counterintuitive, as concluded by researchers from the MESA+ institute for Nanotechnology of the University of Twente. They have succeeded to imitate the weak-interactions in a model system, and publish there findings this week in the authoritative journal Proceedings of the National Academy of Sciences (PNAS)
A virus recognizes a cell by recognition points with which the cell normally communicates with its environment. The virus couples in this process to multiple points via weak-interactions that are mutual cooperating. The virus is even capable to distort the cell membrane in order to gain as many interactions as possible. This complex interplay is investigated in a model system by Olga Crespo (PHd) and Choon Woo Lim (PD). Spherical double-walled vesicles are used as model systems for cell membranes. These vesicles are equipped with receptor molecules, comparable to recognition points at the cell membrane. These receptor molecules recognise specific molecules.
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The virus looks for more recognition points, and thereby even distorts the cell membrane |
Loose ends
Those molecules in their turn couple to metal ions. The type of metal determines the strength of the binding. And there a surprising effect comes into play which is completely counter intuitive: a weaker binding metal, such as nickel, gives rise to a high degree of coagulation of the vesicles, while a strong binding metal does not induce coagulation. In their PNAS-publication the authors explain this effect. Copper does not leave “loose ends” because it interacts very strongly and does not leave unoccupied binding sites at the vesicle. Nickel, which binds much weaker, works more “sloppy” and binds in such a way that there are unoccupied binding sites available at the vesicle. This induces the vesicles to clamp to each other because the surfaces “recognise” each other and give rise to multiple interactions, which is also typical for the binding between cell and virus. Simple and small molecules lead, through cooperation, to complex interactions. The research gives thereby much insight into the molecular recognition process, which is also applicable in for instance in chips that recognize proteins.
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Molecules bind to receptors at the surface of the vesicle and copper-ions bind on the other sites of the molecules. Copper binds strong, and does not leave room for “loose ends” that could interact with other vesicles. |
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This is different in the case of nickel, in that case “loose ends” are present, wheter or not with a nickel-ion. |
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That couple to multiple “loose ends” from other vesicles, which causes coagulation of the vesicles. |
The researchers are members of the Molecular Nanofabrication group of prof. Jurriaan Huskens and the Supra Molecular Chemistry & Technology group of prof. David Reinhoud; both are part of the MESA+ institute for nanotechnology of the University of Twente.
The article “Intravesicular and intervesicular interaction by orthogonal multivalent host-guest and metal-ligand complexation” by Choon Woo Lim, Olga Crespo-Biel, Marc C. A. Stuart, David N. Reinhoudt, Jurriaan Huskens and Bart Jan Ravoo will appear in press, and can be found online in the Early Edition van de Proceedings of the National Academy of Sciences of the USA (PNAS), www.pnas.org