Microprotein
A microprotein (miP) is a small protein encoded from small open reading frame (smORF).[1] They are a class of protein with a single protein domain that are related to multidomain proteins.[2] Microproteins regulate larger multidomain proteins at the post-translational level.[3] Microproteins are analogous to microRNAs (miRNAs) and heterodimerize with their targets causing dominant and negative effects. [4] In animals and plants, microproteins have been found to greatly influence the biological processes.[2] Because of microproteins' dominant effects on their targets, microproteins are currently being studied for potential applications in biotechnology.[2]
History
The first microprotein (miP) discovered was during a research in the early 1990s on genes for basic helix–loop–helix (bHLH) transcription factors from a murine erythroleukaemia cell cDNA library.[3] The protein was found to be an inhibitor of DNA binding (Id), and it negatively regulate transcription factor complex.[3] The Id protein was 16 kDa and consisted of a helix-loop-helix (HLH) domain.[2] The microprotein formed bHLH/HLH heterodimers which disrupted the functional basic helix–loop–helix (bHLH) homodimers.[2] The first microprotein discovered in plants was the LITTLE ZIPPER (ZPR) protein.[2] The LTTLE ZIPPPER protein contains a leucine zipper domain but does not have the domains required for DNA binding and transcription activation.[2] Thus, LITTLE ZIPPER protein is analogous to the Id protein.[2] Despite not all proteins being small, in 2011, this class of protein was given the named microproteins because their negative regulatory actions are similar to those of miRNAs.[3]
Evolutionary, the Id protein or proteins similar to Id are found in all animals.[3] In plants, microproteins are only found in higher order.[3] However, the homeodomain transcription factors that belong to the three-amino-acid loop-extension (TALE) family are targets of microproteins, and this homeodomain proteins are conserved in animals, plants, and fungi.[3]
Structure
Microproteins are generally small proteins with a single protein domain.[2][4] The active form of microproteins are translated from smORF.[1] The smORF codons which microproteins are translated from can be less than 100 codons.[1] However, not all microproteins are small, and the name was given because their actions are analogous to miRNAs.[3]
Function
The function of microproteins is post-translational regulators.[3] Microproteins disrupt the formation of heterodimeric, homodimeric, or multimeric complexes.[4] Furthermore, microproteins can interact with any protein that require functional dimers to function normally.[3] The primary targets of microproteins are transcription factors that bind to DNA as dimers.[5][3] Microproteins regulate these complexes by creating homotypic dimers with the targets and inhibit protein complex function. [3] There are two types of miP inhibitions: homotypic miP inhibition and heterotypic miP inhibition.[4] In homotypic miP inhibition, microproteins interact with proteins with similar protein-protein interaction (PPI) domain.[4] In heterotypic miP inhibition, microproteins interact with proteins with different but compatible PPI domain.[4] In both types of inhibition, microproteins interfere and prevent the PPI domains from interacting with their normal proteins.[4]
References
- ^ a b c "The Dark Matter of the Human Proteome". The Scientist Magazine®. Retrieved 2019-04-25.
- ^ a b c d e f g h i Bhati, Kaushal Kumar; Blaakmeer, Anko; Paredes, Esther Botterweg; Dolde, Ulla; Eguen, Tenai; Hong, Shin-Young; Rodrigues, Vandasue; Straub, Daniel; Sun, Bin (2018-04-18). "Approaches to identify and characterize microProteins and their potential uses in biotechnology". Cellular and Molecular Life Sciences. 75 (14): 2529–2536. doi:10.1007/s00018-018-2818-8. ISSN 1420-682X. PMC 6003976. PMID 29670998.
- ^ a b c d e f g h i j k l Staudt, Annica-Carolin; Wenkel, Stephan (2010-12-10). "Regulation of protein function by 'microProteins'". EMBO Reports. 12 (1): 35–42. doi:10.1038/embor.2010.196. ISSN 1469-221X. PMC 3024132. PMID 21151039.
- ^ a b c d e f g Eguen, T; Straub, D; Graeff, M; Wenkel, S (August 2015). "MicroProteins: small size-big impact". Trends in Plant Science. 20 (8): 477–482. doi:10.1016/j.tplants.2015.05.011. PMID 26115780.
- ^ de Klein, Niek; Magnani, Enrico; Banf, Michael; Rhee, Seung Yon (2015). "microProtein Prediction Program (miP3): A Software for Predicting microProteins and Their Target Transcription Factors". International Journal of Genomics. 2015: 1–4. doi:10.1155/2015/734147. ISSN 2314-436X.
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