Types and effects of protein variations

Abstract

Types and effects of protein variations. Vihinen, MaunoPublished in: Human Genetics DOI: 10.1007/s00439-015-1529-6Published: 2015-01-01Link to publication Citation for published version (APA): Vihinen, M. (2015). Types and effects of protein variations. Human Genetics, 134(4), 405-421. DOI: 10.1007405-421. DOI: 10. /s00439-015-1529 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. for all variation types, a more detailed description can be made by explaining changes to protein function, structure and properties. Examples are provided for the effects and mechanisms, usually in relation to human diseases. In addition, the examples are selected so that protein 3D structural changes, when relevant, are included and visualized. Here, systematics is described for protein variants based on VariO. It will benefit the unequivocal description of variations and their effects and further reuse and integration of data from different sources. 1 TYPES AND EFFECTS OF PROTEIN VARIATIONS

Investigating the linkage between disease-causing amino acid variants and their effect on protein stability and binding

“…Genetic differences can be manifested at different levels as a Single Nucleotide Polymorphism (SNPs), which is a genetic change of single nucleotide or as non‐synonymous SNP (nsSNP), which results in amino acid change in the corresponding transcribed product. In this work we focus on substitutions of single amino acid in the corresponding protein and following the literature such a change is termed single amino acid variation (SAV) . The SAV can affect the corresponding protein's function and thus may be associated with human diseases .…”

Protein dynamics analysis reveals that missense mutations in cancer‐related genes appear frequently on hinge‐neighboring residues

“…Missense mutations can have diverse effects on the properties of proteins such as stability, interaction, and conformational dynamics . Considering the effects of mutations on hinge‐neighboring residues, the most related property is conformational dynamics and allosteric interactions .…”

“…Missense mutations can have diverse effects on the properties of proteins such as stability, interaction, and conformational dynamics. 34,35 Considering the effects of mutations on hinge-neighboring residues, the most related property is conformational dynamics and allosteric interactions. 36,37 As in the example above, a hinge mutation on MAP kinase 1 could bring the protein into its active conformation by affecting the most cooperative mode of motion that facilitates inactive/active conformational transition.…”

Tools for the analysis and characterization of therapeutic protein species

“…Therapeutic proteins designed for clinical use are characterized thoroughly to be able to detect molecular variants which could either be of genetic origin or emerge at the protein level 34 possibly during the manufacturing process and/or storage of the drug. From post-translational modifications (PTMs) to truncated forms to aggregates, which occur during the formulation process or even during administration, protein therapeutics pose problems which need to be carefully monitored.…”