Point Mutation D129G and Calmodulin's Effect of Protein Stability and Structure and its Link to CPVT
Location
CSU Ballroom
Start Date
18-4-2016 10:00 AM
End Date
18-4-2016 11:30 AM
Student's Major
Chemistry and Geology
Student's College
Science, Engineering and Technology
Mentor's Name
Rebecca Moen
Mentor's Department
Chemistry and Geology
Mentor's College
Science, Engineering and Technology
Description
The protein calmodulin (CaM) functions as a ubiquitous calcium (Ca2+) sensing protein and is present in all eukaryotic cell types. In cardiomyocytes (cardiac muscle cells), calmodulin helps mediate Ca2+ homeostasis and binds to Ca2+/calmodulin-dependent protein kinase II (CaMKII). Ca2+/CaM binding to CaMKII in cardiomyocytes leads to phosphorylation of a diverse set of targets including voltage-gated sodium channels, voltage gated potassium channels and the calcium-induced calcium release channels (ryanodine receptors). Numerous cardiac pathologies have been linked to amino acid point mutations in CaM. Early onset severe long QT syndrome (esLQT) is an inherited disorder that causes cardiac episodes that degenerate into ventricular fibrillation, which can cause sudden death. The recurrent cardiac arrest and esLQT has been linked to an aspartic acid to glycine mutation at amino acid residue 129 in CaM (D129G). This mutation is located in the C-terminal lobe of CaM and has been previously shown to decrease Ca2+ affinity of this lobe. Structurally, CaM consists of two lobes: a N-terminal lobe and C-terminal lobe connected by flexible linker. Each lobe can bind two calcium ions. This decreased Ca2+ affinity suggests changes in CaM's ability to bind many of its targets, including CaMKII, which require a Ca2+-bound CaM. Changes in CaM's structural integrity and structural dynamics as well as its interaction with CaMKII are monitored by various biophysical techniques including circular dichroism and thermal denaturation.
Point Mutation D129G and Calmodulin's Effect of Protein Stability and Structure and its Link to CPVT
CSU Ballroom
The protein calmodulin (CaM) functions as a ubiquitous calcium (Ca2+) sensing protein and is present in all eukaryotic cell types. In cardiomyocytes (cardiac muscle cells), calmodulin helps mediate Ca2+ homeostasis and binds to Ca2+/calmodulin-dependent protein kinase II (CaMKII). Ca2+/CaM binding to CaMKII in cardiomyocytes leads to phosphorylation of a diverse set of targets including voltage-gated sodium channels, voltage gated potassium channels and the calcium-induced calcium release channels (ryanodine receptors). Numerous cardiac pathologies have been linked to amino acid point mutations in CaM. Early onset severe long QT syndrome (esLQT) is an inherited disorder that causes cardiac episodes that degenerate into ventricular fibrillation, which can cause sudden death. The recurrent cardiac arrest and esLQT has been linked to an aspartic acid to glycine mutation at amino acid residue 129 in CaM (D129G). This mutation is located in the C-terminal lobe of CaM and has been previously shown to decrease Ca2+ affinity of this lobe. Structurally, CaM consists of two lobes: a N-terminal lobe and C-terminal lobe connected by flexible linker. Each lobe can bind two calcium ions. This decreased Ca2+ affinity suggests changes in CaM's ability to bind many of its targets, including CaMKII, which require a Ca2+-bound CaM. Changes in CaM's structural integrity and structural dynamics as well as its interaction with CaMKII are monitored by various biophysical techniques including circular dichroism and thermal denaturation.
Recommended Citation
Conway, Jacob. "Point Mutation D129G and Calmodulin's Effect of Protein Stability and Structure and its Link to CPVT." Undergraduate Research Symposium, Mankato, MN, April 18, 2016.
https://cornerstone.lib.mnsu.edu/urs/2016/poster-session-A/41
