Microprotein
A microprotein is a small protein encoded from a small open reading frame, also known as sORF-encoded protein. They are a class of protein with a single protein domain. They are related to multidomain proteins. Microproteins regulate larger multidomain proteins at the post-translational level. Microproteins are analogous to microRNAs and heterodimerize with their targets causing dominant and negative effects. In animals and plants, microproteins influence many biological processes. Because of their dominant effects on their targets, microproteins are currently under study for use in biotechnology.
History
The first miP was discovered during a research in the early 1990s on genes for basic helix–loop–helix transcription factors from a murine erythroleukaemia cell cDNA library. The protein was an inhibitor of DNA binding, and negatively regulated the transcription factor complex. The protein was 16 kDa and consisted of a helix-loop-helix domain. The microprotein formed bHLH/HLH heterodimers that disrupted the functional basic helix–loop–helix homodimers.The first plant microprotein discovered was the LITTLE ZIPPER protein. The LITTLE ZIPPER protein contains a leucine zipper domain, but lacks the domains required for DNA binding and transcription activation. Thus, LITTLE ZIPPER protein is analogous to the ID protein. Although not all proteins are small, in 2011, this class of protein was given the name microproteins because their negative regulatory actions are similar to those of miRNAs.
The ID protein or proteins similar to ID are found in all animals. Plant microproteins are only found in higher orders. However, the homeodomain transcription factors that belong to the three-amino-acid loop-extension family are targets of microproteins, and these homeodomain proteins are conserved in animals, plants, and fungi.
Structure
Microproteins generally feature a single protein domain. The active form is translated from smORF. smORFs can be less than 100 codons. However, not all microproteins are small, and the name was given because of the analogy to miRNAs.Despite their short length, Microproteins have been shown to a limited but diverse set of structural folds, but many candidates also show substantial intrinsic disorder; experimentally determined microprotein structures have been solved using approaches including X-ray crystallography, cryo-electron microscopy, and NMR. A computational survey of predicted structures for 44 microproteins reported broadly similar structural characteristics across the set and comparatively few predicted small-molecule ligand-binding sites. Because many structure/disorder predictors are trained primarily on longer “classical” proteins, dedicated workflows and precautions have been proposed for reliable structure and disorder prediction for microproteins.