(230g) Complex Dynamics of Integrin Inserted Domain Unfolding Studied by Optical Tweezer | AIChE

(230g) Complex Dynamics of Integrin Inserted Domain Unfolding Studied by Optical Tweezer

Authors 

Zhang, C. - Presenter, Harvard Medical School
Dill, J. - Presenter, University of Berkeley
Smith, S. B. - Presenter, University of Berkeley
Marqusee, S. - Presenter, University of Berkeley
Bustamante, C. - Presenter, University of Berkeley
Springer, T. A. - Presenter, Department of Pathology, Harvard medical school
Cecconi, C. - Presenter, University of Berkeley
Zhang, F. X. - Presenter, Department of Pathology, Harvard medical school


Integrins are cell adhesion receptors that link to the cytoskeleton and the extracellular matrix, and transmit signals bidirectionally across the cell membrane. Signal transduction between the cytoplasmic domain and the ligand-binding domain (the "Inserted" or I-domain) occurs by a series of conformational changes that lead to allosteric transitions in the I-domain. Different allosteries of the I-domain have markedly different binding affinities for ligands and are critical for cell motility and adhesion. In addition, the I-domain bears the Rossmann fold, a common motif found in nucleic-acid binding proteins and von Willebrand factor A domains, which has a characteristic of inner beta strands being connected by peripheral alpha helices in an alternating matter.

We have performed single molecule pulling experiments on the integrin LFA-1 I-domain using mini optical tweezers. In pulling experiments, mechanical unfolding and refolding revealed 2 or more transitions for the native state to unfold. To further study the dynamics of transitions between different intermediate states we did force clamping experiments in which I-domain single-molecule construct was held at constant force and the time evolution of end-to-end distance was recorded. Force-clamping experiments showed 3 or more intermediate states with complicated dynamics. Here I present our analysis of the force clamping data based on statistics of local fluctuations in the extension. This allows us to characterize the different features of the intermediate states beyond the one-dimensional extension spectra and to sketch an energy landscape that reveals the different states and transitions inbetween.

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