Proteome

The proteome is the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time. More specifically, it is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. The term is a blend of proteins and genome. Proteomics is the study of the proteome.

Systems

The term has been applied to several different types of biological systems. A cellular proteome is the collection of proteins found in a particular cell type under a particular set of environmental conditions such as exposure to hormone stimulation. It can also be useful to consider an organism's complete proteome, which can be conceptualized as the complete set of proteins from all of the various cellular proteomes. This is very roughly the protein equivalent of the genome. The term "proteome" has also been used to refer to the collection of proteins in certain sub-cellular biological systems. For example, all of the proteins in a virus can be called a viral proteome.

History

Marc Wilkins coined the term proteome [1] in 1994 in a symposium on "2D Electrophoresis: from protein maps to genomes" held in Siena in Italy. It appeared in print in 1995,[2] with the publication of part of Wilkins's PhD thesis. Wilkins used the term to describe the entire complement of proteins expressed by a genome, cell, tissue or organism.

Size and contents

The proteome is larger than the genome, especially in eukaryotes, in the sense that there are more proteins than genes. This is due to alternative splicing of genes and post-translational modifications like glycosylation or phosphorylation.

Moreover the proteome has at least two levels of complexity lacking in the genome. While the genome is defined by the sequence of nucleotides, the proteome cannot be limited to the sum of the sequences of the proteins present. Knowledge of the proteome requires knowledge of (1) the structure of the proteins in the proteome and (2) the functional interaction between the proteins.

The unknown ("dark") proteome. Perdigão and co-workers surveyed the “dark” proteome – that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, they found that 44–54% of the proteome in eukaryotes and viruses was "dark", compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage.[3]

Methods to study the proteome

Main article: Proteomics

Numerous methods are available to study proteins, sets of proteins, or the whole proteome. In fact, proteins are often studied indirectly, e.g. using computational methods and analyses of genomes. Only a few examples are given below.

Separation techniques and electrophoresis

Proteomics, the study of the proteome, has largely been practiced through the separation of proteins by two dimensional gel electrophoresis. In the first dimension, the proteins are separated by isoelectric focusing, which resolves proteins on the basis of charge. In the second dimension, proteins are separated by molecular weight using SDS-PAGE. The gel is dyed with Coomassie Brilliant Blue or silver to visualize the proteins. Spots on the gel are proteins that have migrated to specific locations.

Mass spectrometry

Mass spectrometry has augmented proteomics.[4] Peptide mass fingerprinting identifies a protein by cleaving it into short peptides and then deduces the protein's identity by matching the observed peptide masses against a sequence database. Tandem mass spectrometry, on the other hand, can get sequence information from individual peptides by isolating them, colliding them with a non-reactive gas, and then cataloguing the fragment ions produced.

In May 2014, a draft map of the human proteome was published in Nature.[5] This map was generated using high-resolution Fourier-transform mass spectrometry. This study profiled 30 histologically normal human samples resulting in the identification of proteins coded by 17,294 genes. This accounts for around 84% of the total annotated protein-coding genes.

Protein complementation assays and interaction screens

Protein fragment complementation assays are often used to detect protein–protein interactions. The yeast two-hybrid assay is the most popular of them but there are numerous variations, both used in vitro and in vivo.

See also

References

  1. ↑ Wilkins, Marc (Dec 2009). "Proteomics data mining". Expert review of proteomics (England) 6 (6): 599–603. doi:10.1586/epr.09.81. PMID 19929606.
  2. ↑ Wasinger VC, Cordwell SJ, Cerpa-Poljak A, Yan JX, Gooley AA, Wilkins MR, Duncan MW, Harris R, Williams KL, Humphery-Smith I. (1995). "Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium". Electrophoresis 7 (1): 1090–94. doi:10.1002/elps.11501601185. PMID 7498152.
  3. ↑ Perdigão, Nelson; Heinrich, Julian; Stolte, Christian; Sabir, Kenneth S.; Buckley, Michael J.; Tabor, Bruce; Signal, Beth; Gloss, Brian S.; Hammang, Christopher J.; Rost, Burkhard; Schafferhans, Andrea; O'Donoghue, Seán I. (2015). "Unexpected features of the dark proteome". PNAS 112 (52): 15898–15903. doi:10.1073/pnas.1508380112.
  4. ↑ Altelaar, AF; Munoz, J; Heck, AJ (January 2013). "Next-generation proteomics: towards an integrative view of proteome dynamics.". Nature Reviews Genetics 14 (1): 35–48. doi:10.1038/nrg3356. PMID 23207911.
  5. ↑ Kim, Min-Sik; et al. (May 2014). "A draft map of the human proteome". Nature 509 (7502): 575–81. doi:10.1038/nature13302. PMID 24870542.

External links

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