2015-11-22

Cell Biology
Lecture 223.17: Intracellular Compartments and
Protein Sorting

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Protein Trafficking

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Protein Trafficking - Signals

signal peptide

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Protein Trafficking - Signal Hypothesis

Protein Trafficking - Gated

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Protein Trafficking - Gated

Selective cage
Small molecules
diffuse freely
Macromolecules
actively transported

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Protein Trafficking - Signals

Targeting Signals in the Protein
(1) Signal Peptide
15-60 Aa
Anywhere in sequence
Bind to receptor on organelle
Cleaved by signal peptidase
E.g. nuclear localization signal (4-8 aa)
-Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val(Table 15-3)

Protein Trafficking - Gated

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Protein Trafficking - Gated

Protein Trafficking - Gated

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Protein Trafficking

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Protein Trafficking -Transmembrane

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Protein Trafficking -Transmembrane

Transmembrane Transport
E.g.1 Cytosol to ER
Smooth ER:
-no ribosomes
-lipid synthesis
-detoxification
Rough ER:
-studded with ribosomes
-involved in synthesis of proteins
carrying an ER import signal*
-specifically, synthesis of proteins for
endomembrane system (other ER and
organelles)
and cell surface

Protein Trafficking - Signals

Targeting Signals in the Protein
(1) Signal Peptide
15-60 AAs
Bind to receptor on organelle
Cleaved by signal peptidase
E.g. Import to ER (N-terminus)
+H

3N-Met-Met-Ser-Phe-Val-Ser-

Leu-Leu-Leu-Val-Gly-Ile-LeuPhe-Trp-Ala-Thr-Glu-Ala-GluGln-Leu-Thr-Lys-Cys-Glu-Val-PheGln(Table 15-3)

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Protein Trafficking -Transmembrane

Proteins with no ER signal remain in cytosol

Two types of ribosomes in cytosol:

1. Membrane-bound ribosomes (attached to ER) next slide
2. Free ribosomes (unattached to any membrane) see above
Polyribosome = a complex of mRNA + 2 or more ribosomes (can be
free or bound)

Protein Trafficking -Transmembrane

When a ribosome makes a

protein with a ER signal
sequence (red),
the signal
sequence directs
the ribosome
to the ER
membrane

At the end of each

round, the ribosome
subunits rejoin the
common pool

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Protein Trafficking -Transmembrane

Two components guide the ER signal sequence: 1. Signal recognition particle (SRP)
and 2. SRP receptor

Protein Trafficking -Transmembrane

Soluble protein has signal sequence

(or protein translocator)

Note: bound ribosome is present but not shown

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Protein Trafficking -Transmembrane: Single Pass

Single-pass transmembrane protein with start and stop
transfer sequences

Single pass-Glycophorin

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Protein Trafficking -Transmembrane: Double Pass

Fig 15-17 A double-pass transmembrane protein has an

internal ER signal sequence

Protein Trafficking -Transmembrane: Multi Pass

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Protein Trafficking -Transmembrane

Transmembrane Transport
Once in the ER, proteins can
be further shuttled to other
locations
But what if it is supposed to
stay in the ER?
Signal sequence for ER
retention
-Lys-Asp-Glu-Leu-COO-

Protein Trafficking -Transmembrane: Peroxisomes

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Protein Trafficking -Transmembrane: Peroxisomes

Import signal sequence

-Ser-Lys-Leu-COO-

Import of proteins from

cytosol is mediated by a 3 aa
signal at the C-terminus of the
protein (see above)

Protein Trafficking

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