AI Article Synopsis
- - Talin is a protein that helps cells attach to their environment, and its function is influenced by a protein called RIAM, which directs it to specific locations in the cell where force changes its shape to recruit another protein, vinculin.
- - The part of talin known as the R3 domain has two states: when it's closed, it binds to RIAM, and when it's open, it binds to vinculin, indicating a conformational switch that reacts to mechanical pressure.
- - Experiments show that the R3 domain is only partially closed under pressure, and a specific mutant of R3, while binding to RIAM similarly to the normal version, is more stable when closed. This suggests that the R3 domain
Article Abstract
Talin mediates attachment of the cell to the extracellular matrix. It is targeted by the Rap1 effector RIAM to focal adhesion sites and subsequently undergoes force-induced conformational opening to recruit the actin-interacting protein vinculin. The conformational switch involves the talin R3 domain, which binds RIAM when closed and vinculin when open. Here, we apply pressure to R3 and measure H, N, and C chemical shift changes, which are fitted using a simple model, and indicate that R3 is only 50% closed: the closed form is a four-helix bundle, while in the open state helix 1 is twisted out. Strikingly, a mutant of R3 that binds RIAM with an affinity similar to wild-type but more weakly to vinculin is shown to be 0.84 kJ mol more stable when closed. These results demonstrate that R3 is thermodynamically poised to bind either RIAM or vinculin, and thus constitutes a good mechanosensitive switch.
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| http://dx.doi.org/10.1016/j.str.2017.10.008 | DOI Listing |
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