Proteoforms are the diverse protein molecules produced from a single gene whose primary sequence and composition can be diversified by genetic, transcriptomic, translational and post-translational variation. This Review synthesizes technologies and network ap…
Proteoforms are the diverse molecular protein species produced from a single gene through genetic variation, alternative splicing and post-translational modifications. They are the crucial link between genotype and phenotype. There are estimated to be more than one million distinct protein variants produced from ~20,000 protein-coding genes in a given cell, making these proteoforms a vast and largely uncharacterized dimension in biomedical research. This Review focuses on the role of proteoforms in human genetic diseases. We highlight cutting-edge technologies for the identification and characterization of proteoforms, including long-read transcriptomics and emerging methods for direct protein sequencing, and we present a network biology framework to explain how proteoforms can perturb the molecular interactions and cellular pathways underlying disease phenotypes. We believe that precision medicine will require precision proteomics. An increasing knowledge of proteoform biology from molecular, systems and clinical perspectives will guide future research, ultimately contributing to a more precise understanding of the molecular basis of disease and refined therapeutic interventions.
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Източник: Nature.com
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