without pics assignment protein sorting and targeting

8/7/2019 Without Pics Assignment Protein Sorting and Targeting

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PROTEIN SORTING and/or

PROTEIN TARGETING

A typical mammalian cell contains up to 10,000 different kinds of proteins; a

yeast cell, about 5000. For a cell to function properly, each of its numerous proteins must be localized to the correct cellular membrane or aqueous compartment e.g., the

mitochondrial matrix, chloroplast stroma, Lysosomal lumen, or cytosol. Hormonereceptor proteins, for example, those that must be delivered to the plasma membrane ifthe cell is to recognize hormones, and specific ion-channel and transporter proteins are

needed if the cell is to import or export the corresponding ions and small molecules.Water-soluble enzymes such as RNA and DNA polymerases must be targeted to the

nucleus; still others, such as proteolytic enzymes or catalase, must go to Lysosomes or

peroxisomes, respectively. Many proteins, such as hormones and components of the extracellular matrix, must be directed to the cell surface and secreted.

The process of directing each newly made polypeptide to a particular destination

referred to as protein targeting or protein sortingand is critical to the organization and

functioning ofeukaryotic cells. This process occurs at several levels.

Protein targetingis necessary for proteins that are destined to work outside the

cytoplasm.

Protein targeting is more complex in eukaryote because of the presence of many

intracellular compartments.

Prokaryotic protein targeting (secretion):

The chaperone protein SecB binds to the nascent polypeptide chain to prevent

premature folding which would make transport across the plasma membrane impossible.

SecE and SecY are transmembrane components which form a pore in the membrane

through which the still unfolded polypeptide is threaded. The translocation process isenergy-dependent (ATP) and is driven by SecA. Once the protein has passed through the

pore, the signal sequence is cleaved off by an extra cellular, membrane-boundprotease.

Eukaryotic Protein Targeting:

The signals involved in protein sorting are also called sorting signals. They areregions on the targeted protein with certain amino acid sequences. These signals interact

with specific receptors, either on the target organelle or a carrier protein. In the absence

of targeting signals, a protein will remain in the Cytoplasm. Examples include;


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Translational machinery

Metabolic enzymes

Cytoskeletal proteins

Many signal transduction proteins

But targeting in eukaryotes is necessarily more complex due to the multitude ofinternal compartments. There are two basic forms of targeting pathways, viz;

Post translational targeting:

1. Nucleus

2. Mitochondria3. Chloroplasts

4. peroxisomes

Co-translational targeting or Secretary pathway:

1. Endoplasmic reticulum(ER)

2. Golgi Complex3. Lysosomes

4. Plasma membrane

5. Secreted proteins

Post translational targeting:

Post translational targeting includes;

Nuclear targeting:

Nuclear targeting is unusually done by two-way traffic, i.e. transporting inincludes proteins, transcription factors histones etc. and outare mRNA, tRNA, rRNA.

Proteins are not transported through the nuclear membrane but rather through

complex pore called Nuclear pore, comprising of about 100 different proteins. Smaller proteins move through pores by diffusion and larger move by selective transport, or

Nuclear Localization Signal. It is a cluster of positively charged amino acids, e.g.PKKKRLV. Signal sequence binds to receptor on the pore calledImportin.

Mitochondrial and Chloroplast targeting:

Mitochondrial targeting is not well understood and usually done by post-

translational targeting.

Co-translational targeting or Secretary pathway:

Lysosomal targeting:

Lysosomes are organelles that store enzymes which rapidly degrade other proteins

and nucleic acids. A famous target sequence is "KDEL" Initial targeting is viasecretary

pathway.Final targetingoccurs in the Golgi complex.


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Endoplasmic reticulum targeting:

It is co-translational insertion of protein into or through ER membrane via

ribosome (RER).

A signal sequence of 16-30 with some hydrophobic amino acids atN-terminus of

nascent protein on free ribosomes binds tosignal recognition particle (SRP), which haltsthe translation. SRPs consist of 6 proteins and one 7S RNA molecule. The SRP-signal

sequence-mRNA-ribosomes complex docks with receptor of ER membrane and signal

sequence crosses the ER membrane. Now translation continues with polypeptide chain,i.e. being pulled into the lumen of ER. While in the ER, many proteins undergo the first

stages of Glycosylation. Most proteins then migrate inside vesicles from the ER and enter

the cis face of Golgi complex where furtherprocessingand finalsortingoccurs.

The Golgi Complex:

The Golgi is responsible for furtherprocessingand finalsortingof proteins. One

example is the formation ofprimary andsecondaryLysosomes. Primary Lysosomes bud

from the trans face of the Golgi complex and subsequently undergo exocytosis (A), fusewith vesicles to digest their contents (B & C), rupture, causing autolysis (D).

CONCLUSION Targeting of newly synthesized proteins is an integral component of protein synthesis.

In prokaryotes, targeting is usually achieved by an N-terminal signal sequence ofabout 20 mostly hydrophobic amino acids.

In eukaryotes, targeting is more complex due to the large number of different cellular

compartments.

Nuclear targeting is done via the nuclear pore using a nuclear localization signal.

ER targeting is done via N-terminal signal sequences using SRPs with subsequent

attachment to the ER.

Targeting is followed by transport to the Golgi complex.

Protein degradation of damaged or obsolete proteins is carried out by Lysosomes,

vesicles filled with degradating enzymes in an ubiqutin-dependent process by specific

proteases in a large cytosolic complex called theproteasome.

REFERENCES:

Book: Molecular Cell BiologyAuthors: Harvey Lodish Arnold Berk S. Lawrence Zipursky Paul

Matsudaira David Baltimore James E. Darnell

http://bass.bio.uci.edu/%7Ehudel/bs99a/lecture27/lecture8_2b.html

without pics assignment protein sorting and targeting

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