Student: Avani Pisapati
Project: Characterization of the binding affinity between the lynx protein and neuronal nicotinic acetylcholine receptors
View: Research Poster (PDF) | Presentation (YouTube)
Department: Bioengineering
Advisor: Frank Zhang
Abstract
Anxiety disorder is one of the most prevalent psychiatric illnesses in the United States. The lynx family proteins, a subset of the Ly6/uPAR superfamily expressed in multiple regions of the brain, have been shown to modulate the cholinergic system and be involved in the pathogenesis of anxiety disorders. To characterize the mechanism, we studied the interaction between lynx family proteins and neuronal nicotinic acetylcholine receptors (nAChRs). The binding affinity between lynx1 and α4β2-nAChRs and lynx2 and α7-nAChRs were characterized using atomic force microscopy (AFM). The result shows that the rupture forces between lynx1 and α4β2-nAChRs were relatively low (10-40 pN), indicating the binding might not be stable. Fitting the dynamic force spectrum (DFS) to the Bells-Evans model [1] yielded an activation barrier width of 0.92 nm and koff of 0.59 s-1. In contrast, the binding strength between lynx2 and α7-nAChRs was stronger, ranging from 60 to 90 pN. The lynx2-nAChR interaction has an activation barrier width of 0.61 nm and koff of 6.8 x 10-4 s-1 These results indicate that the lynx proteins (lynx1 and lynx2) can bind with nAChRs specifically. However, the lynx2 interaction is stronger and presumably more stable. Ongoing experiments will further identify the structural and biophysical mechanisms underlying lynx-nAChR interactions.
About Avani Pisapati
Avani Pisapati is a second-year M.S. student in the bioengineering department at Lehigh. At the moment, she uses atomic force microscopy and fluorescence microscopy to study single molecules under the mentorship of Dr. Frank Zhang. Molecules her team has researched include the clotting factor von Willebrand factor and the prototoxin lynx, a modulator of nicotinic acetylcholine receptors in the brain.