Protein folding

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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 the process by which a protein gets its functional shape or 'conformation'. It is mainly a self-organising process. Starting from a random coil, polypeptides fold into their characteristic working shape.[1] 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).[2]

Without its correct three-dimensional structure a protein does not work. However, some parts of proteins may not fold: this is normal.[3]

If proteins do not fold into their native shape, they are inactive and are usually toxic. Several diseases are believed to result from misfolded proteins.[4] Many allergies are caused by the folding of the proteins, for the immune system does not produce antibodies for all possible protein structures.[5]

Chaperones[change | edit source]

Chaperonins are large proteins which help the folding of some proteins after synthesis.[6] Chaperones in general were first discovered helping histones and DNA join up to form nucleosomes.[7] Nucleosomes are the builing blocks for chromosomes. It is now clear that this is the way many cell organelles are built up.[8][9]

References[change | edit source]

  1. 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.
  2. Anfinsen C. (1972). "The formation and stabilization of protein structure". Biochem. J. 128 (4): 737–49. PMC 1173893. PMID 4565129.
  3. 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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=stryer%5Bbook%5D+AND+215168%5Buid%5D&rid=stryer.chapter.280.
  4. Selkoe, Dennis J. (2003). "Folding proteins in fatal ways". Nature 426 (6968): 900–904. doi:10.1038/nature02264. PMID 14685251. http://www.nature.com/nature/journal/v426/n6968/full/nature02264.html.
  5. Alberts, Bruce et al 2010. Protein structure and function. In Essential cell biology. 3rd ed, New York: Garland Science, 120-170.
  6. Hartl F.U. 1996. Molecular chaperones in cellular protein folding. Nature 381, 571–579
  7. Ellis R.J. 1996. Discovery of molecular chaperones. Cell stress chaperones 1 (3): 155–60.
  8. 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
  9. 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]