SMBp Group Meeting: Phu Tang (CCM)

Tuesday Sep 5, 2023, 2:00 PM → 3:00 PM America/New_York

3rd Floor Classroom/3-Flatiron Institute (162 5th Avenue)

Speaker: Phu Tang (CCM)

 

Topic: Molecular Dynamics Simulations and Cryo-EM data reveal the intrinsic asymmetry in TMEM16A

Abstract: The TMEM16A (Ca2+-activated Chloride channel) is a membrane protein that plays a vital role in several bodily functions, including pain sensation and fluid secretion. A team of researchers led by Yifan Cheng used cryo-EM to uncover the structure of TMEM16A. However, much remains unknown about how TMEM16A is structurally activated to conduct chlorides after binding to Calciums. One isoform of TMEM16A, which opens more easily because it is less sensitive to membrane potential, displays an asymmetric configuration that is thought to be a critical transition. Through MD simulations, we have characterized this asymmetry configuration. Interestingly, our findings suggest that the distribution of PIP2, a lipid molecule, may be asymmetrical upon binding to TMEM16A. Going forward, we hope to gain further insight into the relationship between PIP2 distribution and the asymmetric TMEM16A configuration so that we can better understand its mechanism to design better therapeutics