Xiphophorous LARP6 La Motif: To Bind or not to Bind
Faculty Mentor Information
Lisa Warner
Presentation Date
7-2017
Abstract
Fibrosis is a serious disease that causes extra deposition of connective tissue that can lead to loss of function of a given system in the human body. The main protein found in fibrotic tissues is Type I collagen. The type I collagen mRNA is synthesized in the nucleus and transferred to the rough ER with the help of LARP6. The major mRNA binding domains found in LARP6 are the La Motif (LaM) domain and an (RNA Recognition Motif) RRM domain. We hypothesize that if we can disrupt the binding activity of LARP6 with type I collagen mRNA, then we can disrupt the synthesis of the type I collagen protein. Understanding how LARP6 interacts with mRNA will inform drug design efforts that can help reduce or eliminate fibrosis. Here, we optimized protein expression in an E. coli platform to produce isotope enriched LaM for Nuclear Magnetic Resonance (NMR) studies. NMR spectra will be used to map the RNA binding surface onto LARP6 LaM and to compare structural features between LARP6s from different species. This information we help us to better understand the LaM domain in LARP6.
Xiphophorous LARP6 La Motif: To Bind or not to Bind
Fibrosis is a serious disease that causes extra deposition of connective tissue that can lead to loss of function of a given system in the human body. The main protein found in fibrotic tissues is Type I collagen. The type I collagen mRNA is synthesized in the nucleus and transferred to the rough ER with the help of LARP6. The major mRNA binding domains found in LARP6 are the La Motif (LaM) domain and an (RNA Recognition Motif) RRM domain. We hypothesize that if we can disrupt the binding activity of LARP6 with type I collagen mRNA, then we can disrupt the synthesis of the type I collagen protein. Understanding how LARP6 interacts with mRNA will inform drug design efforts that can help reduce or eliminate fibrosis. Here, we optimized protein expression in an E. coli platform to produce isotope enriched LaM for Nuclear Magnetic Resonance (NMR) studies. NMR spectra will be used to map the RNA binding surface onto LARP6 LaM and to compare structural features between LARP6s from different species. This information we help us to better understand the LaM domain in LARP6.