Cookies Policy
X

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies.

I accept this policy

Find out more here

Conformational diseases and the protein folding problem: Evidence for species-independent link between protein folding and genetic code degeneracy in ribosomal proteins

No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
The full text of this article is not currently available.

Brill’s MyBook program is exclusively available on BrillOnline Books and Journals. Students and scholars affiliated with an institution that has purchased a Brill E-Book on the BrillOnline platform automatically have access to the MyBook option for the title(s) acquired by the Library. Brill MyBook is a print-on-demand paperback copy which is sold at a favorably uniform low price.

Access this article

+ Tax (if applicable)
Add to Favorites
You must be logged in to use this functionality

image of Biogenic Amines

The family of conformational diseases is expanding rapidly, including not only neurodegenerative conditions like Alzheimer's and Parkinson's diseases, but also certain autoimmune diseases and cancers. The corresponding pathologies have in common their link to misfolded proteins, which accumulate in the cytosol, the rough ER or built up extracellularily, thereby inducing apoptosis, abolishing cell to cell communication, eliciting the immune response or cancelling proper enzymatic (i.e. tumour suppressor) activities. Understanding the mechanism leading to protein misconformation is essential for early diagnosis, efficient therapy and reliable prognosis of these devastating conditions. In previous articles, we showed that, in addition to the primary sequence, an important determinant of the protein structure is the local translation rate, controlled mainly by the choice of synonymous codons along the coding sequence. We found that in coding sequences of E. coli, amino acids having a propensity to appear in particular secondary structures are located in surroundings strongly constraint in fast, or slowly translated codons. To extend this observation to other species, we analyse here all ribosomal protein genes in four species (H. sapiens, S. cerevisiae, B. subtilis and E. coli), for constraints of particular amino acids within sequences of 5 to 21 codons, translated fastest or slowest on average. Although the species investigated make rather different usage of synonymous codons, each species utilizes its synonymous codon repertoire so as to achieve amino-acid constraints in these sequences similar to those observed in E. coli. This suggests that the amino-acid constraints within gene sequences translated at extreme rates are biological invariants to which the species have to conform. Although the constraints are more relaxed in sequences translated at less extreme rates, the general conclusion is that the local translation rate makes, at places at least, important contributions to the protein conformation. Conversely, modifications the local translation rate can at places interfere with native folding and lead to misfolding. Such modifications could be the consequence of spontaneous defects in the translation machinery of the cell, or of its unscheduled, excessive solicitation. This may be one of the routes to conformational diseases.

10.1163/1569391041501753
/content/journals/10.1163/1569391041501753
dcterms_title,pub_keyword,dcterms_description,pub_author
6
3
Loading
Loading

Full text loading...

/content/journals/10.1163/1569391041501753
Loading

Data & Media loading...

http://brill.metastore.ingenta.com/content/journals/10.1163/1569391041501753
Loading

Article metrics loading...

/content/journals/10.1163/1569391041501753
2004-06-01
2016-12-07

Sign-in

Can't access your account?
  • Tools

  • Add to Favorites
  • Printable version
  • Email this page
  • Subscribe to ToC alert
  • Get permissions
  • Recommend to your library

    You must fill out fields marked with: *

    Librarian details
    Your details
    Why are you recommending this title?
    Select reason:
     
    Biogenic Amines — Recommend this title to your library
  • Export citations
  • Key

  • Full access
  • Open Access
  • Partial/No accessInformation