Small proteins are a diverse fold class of proteins (usually <100 amino acids long).[1][2][3] Their tertiary structure is usually maintained by disulphide bridges,[4] metal ligands,[5] and or cofactors such as heme. Some small proteins serve important regulatory functions by direct interaction with certain enzymes and are therefore also an interesting tool for biotechnological applications in microorganisms. [6]

Identification of small proteins

The size of small proteins has limited their identification and characterization for a long time. However, the various examples of functionality have led to the development of methods for their identification.

For larger ORFs, computational identification is based solely on their long uninterrupted coding potential. Computational searches for small proteins take into account multiple parameters, such as the presence of a ribosome binding site and amino acid conservation. [7] RNA sequencing or mass spectrometric data sets available are also incorporated into computational predictions. [8][9]

A method extensively used for the identification of small proteins is ribosome profiling (Ribo-seq or ribosome footprinting). Ribosome profiling uses next generation sequencing and targets only mRNA sequences protected by the ribosomes. Binding of a ribosome on an mRNA suggests that the transcript is being actively translated, allowing for the identification even of very small ORFs.[10]

Mass spectrometry is the best method thus far for identifying small proteins, but their sizes again pose a barrier. However, several adjustments are possible to perform to improve detection and data quality.[11]

See also

References

  1. ↑ Kihara D, Skolnick J (December 2003). "The PDB is a covering set of small protein structures". Journal of Molecular Biology. 334 (4): 793–802. CiteSeerX 10.1.1.333.477. doi:10.1016/j.jmb.2003.10.027. PMID 14636603.
  2. ↑ Su M, Ling Y, Yu J, Wu J, Xiao J (December 2013). "Small proteins: untapped area of potential biological importance". Frontiers in Genetics. 4: 286. doi:10.3389/fgene.2013.00286. PMC 3864261. PMID 24379829.
  3. ↑ Storz G, Wolf YI, Ramamurthi KS (2014-06-02). "Small proteins can no longer be ignored". Annual Review of Biochemistry. 83 (1): 753–77. doi:10.1146/annurev-biochem-070611-102400. PMC 4166647. PMID 24606146.
  4. ↑ Cheek S, Krishna SS, Grishin NV (May 2006). "Structural classification of small, disulfide-rich protein domains". Journal of Molecular Biology. 359 (1): 215–37. doi:10.1016/j.jmb.2006.03.017. PMID 16618491.
  5. ↑ Berg, J. M. (April 1990). "Zinc fingers and other metal-binding domains. Elements for interactions between macromolecules". The Journal of Biological Chemistry. 265 (12): 6513–6. doi:10.1016/S0021-9258(19)39172-0. PMID 2108957. Archived from the original on 8 May 2022.
  6. ↑ Brandenburg F, Klähn S (2020). "Small but smart: On the diverse role of small proteins in the regulation of cyanobacterial metabolism". Life. 10 (12): 322. doi:10.3390/life10120322. PMC 7760959. PMID 33271798.
  7. ↑ Richardson, E. J.; Watson, M. (2012-03-09). "The automatic annotation of bacterial genomes". Briefings in Bioinformatics. 14 (1): 1–12. doi:10.1093/bib/bbs007. ISSN 1467-5463. PMC 3548604. PMID 22408191.
  8. ↑ Sberro, Hila; Fremin, Brayon J.; Zlitni, Soumaya; Edfors, Fredrik; Greenfield, Nicholas; Snyder, Michael P.; Pavlopoulos, Georgios A.; Kyrpides, Nikos C.; Bhatt, Ami S. (2019-08-22). "Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes". Cell. 178 (5): 1245–1259.e14. doi:10.1016/j.cell.2019.07.016. ISSN 0092-8674. PMC 6764417. PMID 31402174.
  9. ↑ Miravet‐Verde, Samuel; Ferrar, Tony; Espadas‐García, Guadalupe; Mazzolini, Rocco; Gharrab, Anas; Sabido, Eduard; Serrano, Luis; Lluch‐Senar, Maria (2019). "Unraveling the hidden universe of small proteins in bacterial genomes". Molecular Systems Biology. 15 (2): e8290. doi:10.15252/msb.20188290. ISSN 1744-4292. PMC 6385055. PMID 30796087.
  10. ↑ Ingolia, Nicholas T.; Brar, Gloria A.; Rouskin, Silvia; McGeachy, Anna M.; Weissman, Jonathan S. (2012). "The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments". Nature Protocols. 7 (8): 1534–1550. doi:10.1038/nprot.2012.086. ISSN 1750-2799. PMC 3535016. PMID 22836135.
  11. ↑ Ahrens, Christian H.; Wade, Joseph T.; Champion, Matthew M.; Langer, Julian D. (2022-01-18). Henkin, Tina M. (ed.). "A Practical Guide to Small Protein Discovery and Characterization Using Mass Spectrometry". Journal of Bacteriology. 204 (1): e00353–21. doi:10.1128/jb.00353-21. ISSN 0021-9193. PMC 8765459. PMID 34748388.


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