Chapter 26

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Transcript Chapter 26

Chapter 26
Protein Sorting
Chapter Objectives
• Understand the pathways of cotranslational
processing of proteins
– ER, Golgi, Plasma membrane, Lysosomes
• Understand the pathways of posttranslational
processing of proteins
– Mitochondria, Peroxisomes, Nucleus
Overview
• Cytoplasmic proteins
• Mitochondria,
peroxisome, or nuclear
proteins
• Extracellular, lysosomal,
ER proteins
Cell Reminder
ER
Golgi
How do proteins know where to go?
• Signal Peptide
– Sends
proteins to
ER
– No signal, to
the cytosol
• Blobel 1999
Nobel Prize
Some polar
Mature protein
N
Hydrophobic (10-15 aa)
Cleavage site
To the ER!
GDP
GTP
GDP
Oligosaccharides – N-linked
Goodbye ER, Hello Golgi
• Must physically
cross a space.
• COP-coated
vesicles
– Coat protein
complex
• COP-II sends
vesicles to Golgi
Finding a Target
• ARF GTPase
activity activated
at target
– Coat is removed
• Target
– Plasma
membrane
• Nerve cells
– Other organelles
Oops!! Goodbye Golgi, Hello ER
• COP-I
• KDEL sequence in protein
Review
To the Lysosome
• Vesicles bud from Golgi to a variety of places
– Lysosomes
• Termernal glycosylation is mannose 6P
• Destructive
Clathrin-coat
• Another way to
make vesicles
– Dynamin pinches
vesicle
• GTP dependent
– Clathrin-coated
vesicles become
endosomes
• Endosomes can
become or fuse
with lysosomes.
Integral Membrane Proteins
To the Mitochondria
To the Peroxisome
• Peroxisomes are thought to be artifact
organelles
– Oxidation reactions
• Without producing energy
– Break down lipids
– No synthesis of proteins
– PTS1 and PTS2 are signals to import proteins
• PTS1 has a c-terminal SKL tripeptide
To the Nucleus
• Transport proteins
– Proteins and RNA are leaving the nucleus
– Proteins are trying to get into the nucleus
– Some proteins are really big
• Nuclear Pore Complex (nucleoporin)
– Very big allows diffusion of up to 40,000 Da
proteins
– Larger proteins must be accepted by complex
Nuclear Pore Complex
Big Protein Transport
• NLS (nuclear localization signal)
– Very positive charge
• PKKKRKV
• KRxxxxxxxxxxPAAIKKAGQAKKKK
• NES (nuclear export signal)
• Some proteins go both ways
– Heteroribonucleoprotein complex (hnRNP)
• Shuttles mRNA out of nucleus
• Returns to pick up more
• 38 amino acid signal sends it both directions
Entropy and Transport to Nucleus
• Not energy mechanism
innate to nucleoporin
• Uses small GTP/GDP
binding protein Ran
Ran as an Energy Mechanism
Controlling Export/Import