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How does a protein get to the

correct cellular location?


Membrane and organelle proteins
contain targeting (sorting) signals in their
amino acid sequence.
Targeting signals are recognized during
or after the protein is translated - special
machinery recognizes the signal and
translocates the protein to its correct
location

Examples of protein targeting


signals
Target

Usual Signal
Location

Signal
Removed?

SIGNAL

ER

N-terminal
Or internal

(+/-)

6-12 hydrophobic aa
often preceded by 1
or more (+) aas

Mitochondrial
matrix

N-terminal
(multiple)

(+)

Amphipathic helix
20-50 residues with
R/K and
hydrophobic sides

Peroxisome

C-terminal

(-)

Usually S-K-L at Cterminus

Nucleus

Internal

(-)

1 cluster 5 basic
aas or 2 smaller
basic clusters
separated by 10 aa

Proteins are targeted to different


compartments in different ways

Proteins that are


targeted to the
nucleus,
mitochondria,
chloroplasts and
peroxisomes are
synthesized on free
ribosomes as soluble
polypeptides

Proteins that are


targeted to the cell
surface, Golgi and
Lysosomes are
synthesized on
ER membrane
bound ribosomes
and move through
the secretory
pathway

What gets the ribosomes with


secretory protein mRNA's to bind
to the ER membranes?

The ER targeting mechanism


requires two special receptor
proteins:
1. Signal recognition particle (SRP)
2. SRP receptor

Translation of secretory mRNA


begins on free ribosomes
N-terminal signal
sequence emerges
from ribosome tunnel
Signal recognition
particle (SRP) binds
to the emerging signal
sequence from the
ribosome

SRP receptor initiates the interaction of


signal sequences with the ER membrane
Receptor is an a,b dimer b
subunit is an intrinsic
membrane protein
a-subunit initiates binding
of ribosome SRP to ER
membrane

How do intrinsic membrane


proteins get inserted into the
ER membrane?

Topologies of some integral membrane


proteins synthesized on the rough ER

Most cytosolic transmembrane proteins have


an N-terminal signal sequence and an
internal topogenic sequence
Type I protein

A single internal signal-anchor sequence directs


insertion of single-pass Type II transmembrane
proteins

Type II
protein, no
N-terminal
signal
sequence

Multipass transmembrane proteins have


multiple topogenic sequences

Most proteins synthesized in the


Rough ER are glycosylated by a
core oligosaccharide that is linked
to asparagine residues
(N-linked glycosylation)

The
glycosylation
signal is AsnX- (Ser/Thr)

N-linked glycosylation occurs


during protein translocation via
the membrane bound protein
oligosaccharide transferase

Core Glycosylation and Trimming


in the ER lumen

Overview
of secretory
pathway

ENDOPLASMIC RETICULUM

GOLGI

Transport
1.In
2.out

In:
-Early endosome
-Late endosome
-Golgi
-ER

Molecular mechanism of membrane transport

In and out transport

Protein pengikat/coated vesicles


-Clathrin (from golgi and from membrane)
-Copi (from golgi to ER)
-Copii (from ER to golgi)
Sebenarnya protein tersebut sangat beragam keberadaannya

Pembentukan clathrin vesicle


Tersusun atas triskelion protein clathrin

Multi subunit protein adaptin. Adaptin akan berikatan pada clathrin dan
transmembran protein, transmembran reseptor, yang akan menagkap
molekul cargo sehingga disebut Reseptor Cargo. Sedikitnya ada 4 jenis
adaptin dan bersifat spesifik terhadap

Mekanisme terjadinya Budding, dibantu oleh:


1.Reseptor
2.Adaptin
3.Clatrin
4.Dynamin
5.Dynamin complex protein (merusak membran dan atau merubah lipid
membran

Clathrin coat akan dilepas dari budding, auxillin yang merupakan bagian
dari vesicle akan mengaktifasi ATPase, HSP70 yang akan menghidrolisis
clathrin.

Mutasi dynamin tidak mampu membuat budding

Pengontrolan transport membran terjadi dengan teratur karena adanya spesifitias


Protein SNARE dan target GTPases (Rabs).

Ikatan SNAREs bersifat


Helix dan disosiasinya
dibantu oleh NSF (ATPase)
dan ATP

HIV menggunakan cara yang mirip dengan mekanisme docking dan integrasi
membran plasma

Pertanyaan:

Cara dan protein yang berperan dalam Pembentukan vesicle?


Mekanisme dan protein yang terlibat dalam budding?
Protein Pengawalan transport membran?
Fungsi ATP dan GTP dalam transport membran?
Kenapa transport membran bersifat spesifik dan teratur?
sebutkan letak dan fungsi protein SNARE, Sar1 dan Rab?

ER: proses maturasi protein


setelah disinteris oleh ribosom,
penambahan gula pada protein

Golgi:
Penambahan dan
modifikasi oligosakarida
kepada protein
Memproduksi karbohidrat
dan lemak

Mekanisme pembetukan vesikel di ER

lysosom:
- Acid hydrolase
- Memerlukan ATP
-