post-translational modifications to proteins
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Post-translational Modifications to Proteins and their Affecting Form and FunctionThis ppt will helps u to learn something about the Post Translational modificationsTRANSCRIPT
Post-translational Modifications to Proteins
Affecting Form and Function
Contents
Why are proteins modified? GlycosylationMembrane proteinsProteolytic processingPhosphorylation AcetylationSmall Molecule BindingRegulated degradation
Glycosylation
Major form of protein modificationSugars are added in the ER and GolgiMost proteins formed in the ER are
glycoproteinsMany different forms and functions
Initial glycosylation in the ER
A precursor oligosaccharide is formed on a dolichol lipid
This is transferred to the growing protein
Glycosylation and protein folding
by glucosidase
Processing in the Golgi
Functions of glycosylation
Stabilise proteins against proteolysis Limit approach of macromolecules to protein
surface
Modulation of immune response Selectins (weakly) bind to oligosaccharides Helps to concentrate lymphocytes in lymphoid
organs Attracts white blood cells & platelets to
inflammation sites
Functions of glycosylation
Provide sorting signals M6P for lysosomal hydrolases GPI anchors (see later)
Contributes to differentiation events in organism development Removing N-acetylglucoasmine transferase I in
mice causes embryo deathNeural tube development and left-right body plan
asymmetry impaired
Proteoglycans and the Extracellular MatrixMade of core protein and
polysaccharide chains Extremely diverse
Form hydrated gel Resists compressive forces Regulate traffic (perlecan in kidney)
Can regulate secreted protein activity
e.g. chemokines in inflammatory response
Membrane proteins: GPI anchors
GPI-anchored proteins are delivered to the apical plasma membrane
Trypanosomes can shed these proteins to avoid immune attack
Myristylation and Farnesylation
Attaches cytosolic proteins to the plasma membrane
Protein usually involved in signal transduction
Proteolytic processing
Why is this common for secreted enzymes? Some peptides (e.g. enkephalins) too short by
themselves Prevent premature activation of hydrolytic
enzymes
Phosphorylation
Most common posttranslational modification to proteins in eukaryotes
Enzymes and regulators are turned ‘on’ and ‘off’
Energy from ATP
Phosphorylation Regulates Protein Synthesis – eIF-2
Phosphorylation and Molecular Switches
Signalling using GTP-Binding - Ras ProteinBroadcasts signals from cell surface
Cell proliferation Differentiation
Phosphorylation and Motor Proteins
Move chromosomes during mitosis
Move organelles along molecular tracks
Move enzymes along DNA during DNA synthesis
Phosphorylation and Motor Proteins
ATP binding - conformation 1 to conformation 2
ATP hydrolyzed to ADP Pi - conformation 2 to conformation 3.
Release of ADP and Pi - back to conformation 1.
Irreversible – one direction only
Acetylation
Acetylation and Histones
Acetylation enhances transcription
Deacetylation represses transcription
Small Molecule Binding
A. Retinal
B. Heme group
Protein Degradation
Degradation mechanisms: Ubiquitin ligase Degradation signal
Multiubiquitin chain marks protein for degradation in proteosome
Common Post-translational Modifications
Sulphydryls Disulphide bondCysteinylation
OxidationGlutathionylation
Amines Methylation Acetylation Farnesylation Biotinylation Stearoylation
Formylation Lipoic acid Myristoylation Palmitoylation Geranylgeranylation
Acids & amides Pyroglutamic acid Carboxylation
Deamidation
Hydroxyl groups Phosphorylation Sulphation
Carbohydrates Pentoses Hexosamines N-acetylhexosamines
Deoxyhexoses Hexoses Sialic acid
Summary
Post-translational modifications – necessary for protein function Correct protein folding Organism development Cellular Signalling Motor Proteins Regulating degradation …and much more…