chapter 26 protein sorting. chapter objectives understand the pathways of cotranslational processing...
TRANSCRIPT
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Chapter 26
Protein Sorting
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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
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Overview
• Cytoplasmic proteins• Mitochondria,
peroxisome, or nuclear proteins
• Extracellular, lysosomal, ER proteins
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Cell Reminder
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ER
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Golgi
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How do proteins know where to go?
• Signal Peptide– Sends
proteins to ER
– No signal, to the cytosol
• Blobel 1999 Nobel Prize
Some polar
Hydrophobic (10-15 aa)
Mature protein
Cleavage site
N
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To the ER!
GDPGTP
GDP
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Oligosaccharides – N-linked
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Goodbye ER, Hello Golgi
• Must physically cross a space.
• COP-coated vesicles– Coat protein
complex• COP-II sends
vesicles to Golgi
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Finding a Target
• ARF GTPase activity activated at target– Coat is removed
• Target– Plasma membrane
• Nerve cells
– Other organelles
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Oops!! Goodbye Golgi, Hello ER
• COP-I• KDEL sequence in protein
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Review
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To the Lysosome• Vesicles bud from Golgi to a variety of places– Lysosomes• Termernal glycosylation is mannose 6P• Destructive
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Clathrin-coat
• Another way to make vesicles– Dynamin pinches
vesicle• GTP dependent
– Clathrin-coated vesicles become endosomes• Endosomes can
become or fuse with lysosomes.
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Integral Membrane Proteins
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To the Mitochondria
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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
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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
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Nuclear Pore Complex
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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
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Entropy and Transport to Nucleus
• Not energy mechanism innate to nucleoporin
• Uses small GTP/GDP binding protein Ran
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Ran as an Energy Mechanism
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Controlling Export/Import