Protein folding

From Simple English Wikipedia, the free encyclopedia
Protein before and after folding
Protein folding is the third stage in the development of protein structure.
The structure of a chaperonin. Chaperonins assist some protein folding.

Protein folding is how a protein gets its functional shape or 'conformation'. It is mainly a self-organising process.[1] Starting from a random coil, polypeptides fold into their characteristic working shape.[2] The structure is held together by hydrogen bonds.

The stages are:

  1. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any developed three-dimensional structure (left hand side of the top figure).
  2. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (right hand side of the figure). This is known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence (Anfinsen's dogma).[3]

Without its correct three-dimensional structure a protein does not work. However, some parts of proteins may not fold: this is normal.[4]

If proteins do not fold into their native shape, they are inactive and are usually toxic. Several diseases may be caused by misfolded proteins.[5] Many allergies are caused by the folding of the proteins, for the immune system does not produce antibodies for all possible protein structures.[6]

On 30 November 2020, the protein folding was solved by artificial intelligence company DeepMind.[7][8]

Chaperones[change | change source]

Chaperonins are large proteins which help the folding of some proteins after synthesis.[9] Chaperones in general were first discovered helping histones and DNA join up to form nucleosomes.[10] Nucleosomes are the building blocks for chromosomes. This is the way many cell organelles are built up.[11][12]

References[change | change source]

  1. Dobson C.M. 2000. The nature and significance of protein folding. In Pain R.H. (ed) Mechanisms of protein folding. Oxford University Press, 1–28. ISBN 0-19-963789-X
  2. Alberts, Bruce; et al. (2002). "The shape and structure of proteins". Molecular biology of the cell. New York: 4th ed, Garland Science. ISBN 0-8153-3218-1.
  3. Anfinsen C. (1972). "The formation and stabilization of protein structure". Biochem. J. 128 (4): 737–49. doi:10.1042/bj1280737. PMC 1173893. PMID 4565129.
  4. Berg, Jeremy M; Tymoczko, John L. & Stryer, Lubert. Web content by Neil D. Clarke (2002). "3. Protein structure and function". Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
  5. Selkoe, Dennis J. (2003). "Folding proteins in fatal ways". Nature. 426 (6968): 900–904. Bibcode:2003Natur.426..900S. doi:10.1038/nature02264. PMID 14685251. S2CID 6451881.
  6. Alberts, Bruce et al 2010. Protein structure and function. In Essential cell biology. 3rd ed, New York: Garland Science, 120-170.
  7. "DeepMind AI cracks 50-year-old problem of protein folding". The Guardian. 30 November 2020. Retrieved 30 November 2020.
  8. "AlphaFold: a solution to a 50-year-old grand challenge in biology". DeepMind. 30 November 2020. Retrieved 30 November 2020.
  9. Hartl F.U. 1996. Molecular chaperones in cellular protein folding. Nature 381, 571–579
  10. Ellis R.J. 1996. Discovery of molecular chaperones. Cell stress chaperones 1 (3): 155–60.
  11. Bartlett A.L. & Radford S.E. 2009. An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms. Nat. Struct. Mol. Biol. 16, 582–588
  12. Hartl F.U. & Hayer-Hartl M. 2009. Converging concepts of protein folding in vitro and in vivo. Nature Structural & Molecular Biology 16 (6): 574–581. [1]