Ribosomes are the organelles – the term literally means
little organs -that function as the site for protein manufacture within the
cell. The blueprint for the structure of
each unique protein is specified by the cell’s DNA. Once the newly formed protein is complete, it
is released from the ribosome and enters the cellular cytoplasm. Upon release from the ribosomal surface, the
nascent protein must fold into a precise configuration in order to attain full
functionality. This folding process is
spontaneous. However, the many diverse
macromolecules that fill the cytoplasmic intracellular environment can impose a
serious impediment to this folding process.
To meet this challenge, a sophisticated “chaperone” system
is designed to reduce unfavorable interactions with the cytoplasmic environment
in order to enhance the likelihood of successful folding. It does this through a repetitious series of
binding and release. If these repeated
attempts fail, evidence from scientific investigations has shown that the
folding process is ultimately terminated for it may pose a threat to cellular
energy resources and increase the abundance of toxic reactive oxygen species.
The nature of this termination mechanism – using growing
yeast cells as the model organism – has been studied in detail by Dr. Chenchao
Xu and his colleagues from the Temasek Life Sciences Laboratory at the National
University of Singapore. From their
studies, they have shown that the folding process is terminated by a specialized
pathway that utilizes the modification of the unfolded protein by an
enzyme-mediated chemical reaction known as o-mannosylation involving the transfer of mannose – a sugar – to the
serine – an amino acid – residue of the protein. This modification was shown to disable
folding entirely.
Finally, the authors of this study propose that the function
of this mechanism designed to thwart repeated folding attempts is to end
apparently futile chaperone-directed folding.
As mentioned previously, repeated and unsuccessful cycles of folding can
seriously impinge upon cellular energy reserves. The fate of unfolded proteins is their
ultimate degradation.
This kind of study helps to elucidate complex cellular
mechanisms and highlights the importance of maintaining homeostasis within the
cellular environment.
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