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Protein Kinesis: Getting Proteins to Their Destination

Proteins are the major building blocks of life. Eukaryotic cells synthesize proteins for thousands of different functions. Some examples:

All proteins are synthesized by ribosomes using the information encoded in molecules of messenger RNA (mRNA). This process is called translation and is described in Gene Translation: RNA -> Protein. Our task here is to explore the ways that these proteins are delivered to their proper destinations.

The various destinations for proteins occur in two major sets: So the first decision that must be made as a ribosome begins to translate a mRNA into a polypeptide is whether to remain free in the cytosol or to bind to the ER.

Pathways Through the Endoplasmic Reticulum (ER)

The decision to enter the ER is dictated by the presence of a signal sequence on the growing polypeptide.

The Signal Sequence

The signal sequence in many proteins consists of the first portion of the elongating polypeptide chain (so the signal sequence occurs at the amino terminal of the polypeptide). Typical signal sequences contain about 15 amino acids. The precise amino acid sequence varies surprisingly from one protein to the next, but all signal sequences include many hydrophobic amino acids.

The 1999 Nobel Prize in Physiology or Medicine was awarded on October 11, 1999 to Dr. Günter Blobel for his discovery of the signal sequence and other intrinsic signals that enable proteins to reach their proper destinations.

If a signal sequence is present,

Destinations of proteins synthesized within the ER

Proteins synthesized within the ER are transported to the Golgi apparatus. Portions of the ER are pinched off, forming transport vesicles. These carry their load of proteins to the Golgi apparatus. The membrane of the transport vesicle fuses with the membrane of the Golgi apparatus, merging their contents. Further steps of glycosylation may occur within the Golgi apparatus. The exact pattern of glycosylation determines the final destination of the proteins. There are two options.

The Signal Recognition Particle (SRP)

The signal recognition particle in mammalian cells is made from: It contains binding sites for: [Return to signal sequence]

Destinations of Proteins Synthesized By Free Ribosomes

Ribosomes synthesizing a protein without a signal sequence do not bind to the ER and continue synthesis until the polypeptide is completed. Chaperones are also present in the cytosol that help the protein assume its final three-dimensional configuration. Some of the important destinations for these proteins are:
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15 February 2020