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biomol
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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
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 C-
terminus
Nucleus Internal (-) 1 cluster 5 basic
aas or 2 smaller basic clusters
separated by 10 aa
Examples of protein targeting
signals
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
The ER targeting mechanism
requires two special receptor
proteins:
What gets the ribosomes with
secretory protein mRNA's to bind
to the ER membranes?
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 Asn-
X- (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
-