Post-Translational Protein Modifications Overview
Illustrations and explanations of various post-translational modifications of proteins, including phosphorylation, glycosylation, ubiquitination, and more. Learn about the diverse types of modifications and their significance in cellular processes and protein function.
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Presentation Transcript
Activating and de-activating Ras Nancy Griffeth January 15, 2014 Funding for this workshop was provided by the program Computational Modeling and Analysis of Complex Systems, an NSF Expedition in Computing (Award Number 0926200).
Key human members of Ras family KRAS, HRAS, NRAS Kick-start cell growth when activated Other signaling?
Some terms Conserved proteins, genes, etc.: Appear in many organisms, presumably conserved by evolution Allosteric site: a site (other than the catalytic site) that affects the rate of a catalytic reaction Hydrolysis: cleavage of chemical bonds by the addition of water GTPase: a protein that catalyzes hydrolysis of GTP to GDP
A Video: GTPases as Molecular Switches
Turning Ras On and Off Ras is normally tightly bound to GDP Ras is activated by binding to GTP instead of GDP Ras is a weak GTPase (i.e., it encourges hydrolysis of GTP into GDP) A guanine nucleotide exchange factor helps Ras to exchange GTP for GDP GEF is the generic term Sos1 is the specific GEF we will look at A GTPase Activating Protein speeds up Ras GTPase activity GAP is the generic term RASA1 is the specific GAP we will look at
Turning Ras On and Off Ras- GDP Ras-GDP is the off state of Ras
Turning Ras On and Off Ras- GDP Ras- GTP Ras-GTP is the on state of Ras
Turning Ras On and Off Ras- GDP Ras- GTP The entire reversible reaction (????)
Turning Ras On and Off GDP Ras- GDP Ras-O Ras- GTP GTP Ras can bind to either GDP or GTP (or not at all)
Turning Ras On GDP Ras- GDP GEF Ras-O Ras- GTP GTP A guanine nucleotide exchange factor (GEF) helps Ras exchange a GDP for a GTP
Turning Ras On and Off GDP Ras- GDP GAP GEF Ras-O Ras- GTP GTP A GTPase Activating Protein (GAP) helps Ras turn the GTP back into GDP
But wait: Theres More!! Ras- GDP GAP GEF Ras- GTP
How Fast Does Ras Turn On? Ras- GDP Sos1 Ras- GTP
Guanine Nucleotide Exchange Rate Ras- GDP Ras- GDP Cdc25 REM Rate: kcat, Km Part of Sos1 Sos1
Guanine Nucleotide Exchange Rate GDP Ras- GDP Ras-O Cdc25 REM Rate: kcat, Km Part of Sos1 Sos1
Guanine Nucleotide Exchange Rate GTP Ras- GTP Ras-O Cdc25 REM Rate: kcat, Km Part of Sos1 Sos1
Guanine Nucleotide Exchange Rate GDP GTP Ras- GDP Ras- GTP Ras-O Cdc25 REM Part of Sos1 Sos1
Guanine Nucleotide Exchange Rate GDP GTP Ras- GDP Ras- GTP Ras-O Ras- GDP Cdc25 REM Rate: 5 times as fast Part of Sos1 Sos1
Guanine Nucleotide Exchange Rate GDP GTP Ras- GDP Ras- GTP Ras-O Ras- GTP Cdc25 REM Rate: 75 times as fast Part of Sos1 Sos1
Ras Deactivation (Hydrolysis) Ras- GDP RASA1 Ras- GTP
How Fast Does Ras Turn Off Ras- GDP Ras- GTP Ras-GTP is a GTPase: It hydrolyzes GTP to GDP (slowly)
Ras Deactivation (Hydrolysis) Ras- GDP RASA1 Ras- GTP RASA1 speeds up the hydrolysis by ???
Turning Ras On and Off: The Whole Story ( or is it?) GDP Ras- GDP Sos1 slow fast RASA1 Ras-O Super fast Ras- GTP GTP
Summary Ras is normally tightly bound to GDP Ras is activated by binding to GTP instead of GDP A guanine nucleotide exchange factor helps Ras to exchange GTP for GDP GEF is the generic term Sos1 is the specific GEF we will look at Sos1 has an allosteric site that affects the reaction rate A GTPase activating protein speeds up Ras GTPase activity (ie, hydrolyzing the GTP so it becomes GDP) GAP is the generic term RASA1 is the specific GAP we will look at
YouTube Lectures on Ras Wittinghofer Part 1 Wittinghofer Part 2
