Men and women at equal lung cancer risk from smoking
July 25, 2017
To better understand FAK activity, Schaller collaborated with the Structural Bioinformatics Core Facility at UNC to predict the three-dimensional configuration of FAK's FERM domain.
Computer modeling of the FERM domain predicted a small patch of positively charged amino acids on its surface. These amino acids are conserved in the FAK molecules of organisms as diverse as insects and humans.
Schaller and his colleagues then engineered a mutant FAK molecule devoid of positive charges on that small patch of FERM and found that their mutant protein was nonfunctional. Whereas breast cancer cells responded to increased expression of normal FAK by migrating faster, the mutant
FAK was unable to provoke any change in movement from breast cancer cells."Our mutant appears to be deficient for turning FAK on and making cells move," Schaller said.
The positively charged region identified in this study seems to cooperate directly with other domains of the molecule, he added.
"Disruption of this interaction might reduce activation of FAK and impair aberrant cell motility or survival conferred by FAK under pathological conditions, such as cancer."
The study was supported by grants from the National Institutes of Health and the U.S. Department of Defense.
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