WORLD OF MICROBIOLOGY AND IMMUNOLOGY Protein export453•
PProtein exportROTEIN EXPORT
Protein export is a process whereby protein that has been man-
ufactured in a cell is routed to the surface of the cell. Export
of proteins occurs in all microorganisms, but has been partic-
ularly well-studied in certain species of bacteriaand yeast.
The ability of a cell to export protein is crucial to the
survival or pathogenicity of the cell. Bacteria that have protein
appendages for movement (e.g., flagella) and attachment (e.g.,
pili), and protective protein surface coatings (e.g., S layers)
depend on the efficient export of the proteins. Exotoxins that
are ultimately excreted by some bacteria need to get across the
cell wall before being released from the bacterium.
Defects in protein export can produce or contribute to a
number of maladies in eukaryotic cells including human cells
(e.g., cystic fibrosis, diabetes, osteopororsis).
A general feature of protein export is the manufacture of
a protein destined for secretion in a slightly longer form than
the exported form of the protein. The additional stretch is
known as the signal sequence, and its role in protein export
forms the so-called signal hypothesis. Gunter Blobel garnered
the 1999 Nobel Prize in Physiology or Medicine for his pio-
neering efforts in this area.The “pre-protein” contains sequences of amino acids
that give the precursor stretch of protein blocks that are
hydrophilic (water-loving) and hydrophobic(water-hating).
This allows a portion of the precursor region to spontaneously
bury itself in the membrane layer that surrounds the interior of
a bacterium, or the membrane of the endoplasmic reticulum of
cells such as yeast. The hydrophilic sequences that flank the
hydrophobic region associate with either side of the mem-
brane. Thus, the precursor region is a membrane anchor.
Anchoring of the protein to the membrane is assisted by
the action of two proteins. One of these proteins (designated
SecB) associates with the precursor sequence of the newly
made protein. The SecB protein then recognizes and binds to
a protein called SecA that is embedded in the membrane. The
SecB-SecA complex acts to guide the precursor region into
position at the membrane. As the remainder of the protein is
made, it is pushed out of the opposite side of the membrane.
An enzyme associated with the outer surface of the membrane
can snip off the precursor.
This process is sufficient for protein export in Gram-
negative bacteria that have the single membrane. However, in
Gram-negative bacteria the protein must be transported across
the periplasmand the outer membrane before being truly
exported. Furthermore, yeast cells require additional mecha-Dr. Ergo Novotny examines a model of a protein.womi_P 5/7/03 11:10 AM Page 453