Protein Targeting 1

Protein Targeting:

What Enables a Cell to Tell a Protein Where to Go?

Raven Johnson

Grambling State University

 Protein Targeting 2

Abstract

Protein targeting and how it is done within cells was discussed in this paper. You will

find that for protein targeting to take place many have to be synthesized. The methods in which

proteins are targeted were discussed as well. This paper shares the basic structures of signal

sequences and how they are used. Signal sequences are used by almost every living cell to target

a protein, if not all. Proteins are targeted going to the mitochondria, cytoplasm, nucleus,

lysosomes, as well as many other places. They are targeted using signal sequences in

combination with ribosomes, cytosol, the E.R., and several others. Proteins are also targeted

because they have different parameters. They are targeted based on where they sit in a chain, i.e.

carboxylic terminus, or based on what type of function they may perform, such as secretion.
 Protein Targeting 3

Protein Targeting:

What Enables a Cell to Tell a Protein Where to Go?

Proteins that have specified functions are found in all living cells. Bacteria cells have a

minimum of one membrane to separate the inside of the cell from its surroundings (Dalbey &

von Heijne, 2002). Eukaryotic cells have numerous structures and organelles with unique roles

need specific proteins and enzymes (Nelson & Cox, 2008). At Cold Spring Harbor Laboratory

(1996) found that development in in-vivo systems has made our current understanding of protein

targeting possible. Dalbey and von Heijne estimated in 2002 that in a normal cell almost half of

proteins were carried across a membrane. Most proteins translocate to move across membranes

(Cold Spring Harbor Laboratory Press, 1996)

Proteins going to the nucleus, cytoplasm or mitochondria use three different pathways.

Proteins going to the cytosol stay where they were synthesized and proteins that are carried for

secretion, lysosomes or plasma membranes commonly share the first few steps of a pathway.

This begins in the endoplasmic reticulum (E.R.). The most important part in these pathways is

the signal sequence or a short sequence of amino acids. Signal sequence was first hypothesized

by Günter Blobel and some of his colleagues in 1970 (Nelson & Cox, 2008). The signal

sequence carries the data for targeting a protein into an organelle (Cold Spring Harbor

Laboratory Press, 1996). The signal sequence also tells a protein where to go in the cell and is

usually removed while being transported or after its destination is reached.

Mitochondria and cytoplasts protein targeting rely on amino-terminal signal sequences.

Nelson and Cox (2008) think the nest targeting system is started in the E.R. They also say that

the E.R. has hundreds of signal sequences. The signal sequences help get the ribosomes to the

E.R., and usually consist of between 13 and 36 amino acids. Proteins with short sequences near

the cayboxylic terminus, relatively polar, has one or more positively charged residues near the
 Protein Targeting 4

amino terminus and about 10-15 hydrophobic amino acid residues are synthesized on the

ribosomes of the E.R. (Nelson & Cox, 2008). The signal sequence guides ribosomes to the E.R.

in an eight step process.

“1.The targeting pathway begins with initiation of protein synthesis on free ribosomes. 2.

The signal sequence appears early in the synthetic process because it is at the amino
3.
terminus, which as we have seen is synthesized first. As it emerges from the ribosome,

the signal sequence—and the ribsosome itself—are bound by the large signal recognition

particle (SRP); SRP then binds GTP and halts elongation of the polypeptide when it is

about 70 amino acids long and the signal sequence has completely emerged from the
4.
ribosome. The GTP-bound SRP now directs the ribsosome (still bound to the mRNA)

and the incomplete polypeptide to GTP-bound SRP receptors in the cytosolic face of the

ER; the nascent polypeptide is delivered to a peptide translocation complex in the ER….
5.
SRP dissociates from the ribosome, accompanied by hydrolysis of GTP in both SRP and
6.
the SRP receptor. Elongation of the polypeptide now resumes, with ATP-driven

translocation complex feeding the growing polypeptide in the ER lumen until the
7.
complete protein has been synthesized. The signal sequence is removed by a signal

peptidase within the ER lumen; 8.The ribosome dissociates and is recycled.

Macromolecules, movement through nucleic pores, aid in the communication between the

nucleus and cytosol (Nelson & Cox, 2008). Nuclear pore complexes are enormous structures

and support two way trafficking (Dalbey & von Heijne, 2002). RNA molecules are exported to

the cytosol after being synthesized in the nucleus and ribosomal proteins are imported into the

nucleus and amassed into 60S and 40S ribosomal subunits in the nucleolus after being

synthesized on cytosolic ribosomes. Traffic of this type is adapted by molecular signals and
 Protein Targeting 5

transport proteins in a complex system that gradually expose. The signal sequence that targets a

protein to the nucleus in this process is the nuclear localization sequence.

“1.A protein with an appropriate nuclear localization signal is bound by a complex of

2. 3.
importin α and ß. The resulting complex binds to a nuclear pore, and translocates.
4.
Inside the nucleus, dissociation of importin ß is promoted by the binding of Ran-GTP.

Importin α binds to Ran-GTP and CAS (cellular apoptosis susceptibility protein),

5.
releasing the nuclear protein. importin α and ß and CAS are transported out of the

nucleus and recycled. They are released in the cytosol… 6.Ran-GDP is bound by NTF2,
7.
and transported back into the nucleus. RanGEF promotes the exchange of GDP for

GTP in the nucleus, and Ran-GTP is ready to process another NLS-bearing protein-

importin complex…”

In bacteria, proteins are targeted to the inner or outer membranes, periplasmic space

between the membranes or extracellular medium. They also use amino terminus signal

sequences. This process is give by Nelson and Cox.

“1.A newly translated polypeptide binds to the cytosolic chaperone protein SecB, which
2.
delivers it to the SecA, a protein associated with the translocation complex (SecYEG)…
3.
SecB is released, and SecA inserts itself into the membrane, forcing about 20 amino acid
4.
residues of the protein to be exported through the translocation complex. Hydrolysis of

an ATP by SecA provides the energy for a conformational change that causes SecA to
5.
withdraw from the membrane, releasing the polypeptide. SecA binds another ATP, and

the next stretch of 20 amino acid residues is pushed across the membrane through the
4. 5.
translocation complex. Steps and are repeated until 6.the entire protein has passed

through and is released to the periplasm.”

 Protein Targeting 6

Through this research I have found that the common denominator in any cell protein

targeting is a signal sequence. This hold true even for bacteria cells. The signal sequence is

what tells the cell which protein to target and tells the cell where to send the targeted protein.

Though my research was not extensive enough to tell me everything protein targeting was used

for, I found that it is used for many of life’s basic functions and for the survival of or species.

Each cell type has a different approach to targeting a cell. As you can see I have shared with you

three basic pathways a cell may take.

 Protein Targeting 7

References

Cold Spring Harbor Laboratory Press. (1996). Protein kinesis: the

dynamics of protein trafficking and stability . Europe: Cold Spring

Harbor Laboratory Press.

Dalbey, R. E., & von Heijne, G. (2002). Protein targeting, transport

and translocation. San Diego, CA: Academic Press.

Nelson, D. L., & Cox, M. M. (2008). Lehninger principles of

biochemistry. New York, NY: W. H. Freeman and Company.