Biochemistry on a leash: the roles of tether length and geometry in signal integration proteins.
We use statistical mechanics and simple ideas from polymer physics to develop a quantitative model of proteins whose activity is controlled by flexibly tethered ligands and receptors. We predict how the properties of tethers influence the function of these proteins and demonstrate how their tether length dependence can be exploited to construct proteins whose integration of multiple signals can be tuned. One case study to which we apply these ideas is that of the Wiskott-Aldrich Syndrome Proteins as activators of actin polymerization. More generally, tethered ligands competing with those free in solution are common phenomena in biology, making this an important specific example of a widespread biological idea.
Van Valen
David
D
Department of Applied Physics, California Institute of Technology, Pasadena, California, USA.
Haataja
Mikko
M
Phillips
Rob
R
D000199:Actins / Q000737:chemistry; D000465:Algorithms; D008024:Ligands; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000737:chemistry*; D018909:src Homology Domains
D000199:Actins; D008024:Ligands; D051300:Wiskott-Aldrich Syndrome Protein Family