Abstract
A variety of studies have suggested that low-complexity domains (LCDs) tend to be intrinsically disordered and are relatively rare within structured proteins in the Protein Data Bank (PDB). Although LCDs are often treated as a single class, we previously found that LCDs enriched in different amino acids can exhibit substantial differences in protein metabolism and function. Therefore, we wondered whether the structural conformations of LCDs are likewise dependent on which specific amino acids are enriched within each LCD. Here, we directly examined relationships between enrichment of individual amino acids and secondary structure tendencies across the entire PDB proteome. Secondary structure tendencies varied as a function of the identity of the amino acid enriched and its degree of enrichment. Furthermore, divergence in secondary structure profiles often occurred for LCDs enriched in physicochemically similar amino acids (e.g. valine vs. leucine), indicating that LCDs composed of related amino acids can have distinct secondary structure tendencies. Comparison of LCD secondary structure tendencies with numerous pre-existing secondary structure propensity scales resulted in relatively poor correlations for certain types of LCDs, indicating that these scales may not capture secondary structure tendencies as sequence complexity decreases. Collectively, these observations provide a highly resolved view of structural tendencies among LCDs parsed by the nature and magnitude of single amino acid enrichment.
Highlights
Protein sequence, in combination with surrounding physicochemical environment, fundamentally determines protein form and function
Lowcomplexity domains (LCDs) in protein sequences are unusual regions made up of only a few different types of amino acids. This is the key feature that classifies sequences as low-complexity domains (LCDs), the physical properties of LCDs will differ based on the types of amino acids that are found in each domain
We developed a new method to further divide LCDs into categories that more closely reflect the differences in their physical properties
Summary
In combination with surrounding physicochemical environment, fundamentally determines protein form and function. Proteins with LCDs exhibit differences in metabolic regulation, molecular interaction partners, subcellular localization, and molecular functions [18,20,21], all of which hinge upon the primary amino acid enriched in each LCD [18]. Even LCDs enriched in highly similar amino acids can be associated with specialized molecular functions and distinct trends in metabolic regulation. While both N-rich and Q-rich LCDs are associated with transcription, N-rich domains are associated with P-bodies, whereas Q-rich domains are associated with functions related to endocytosis [18]. While enrichment of most hydrophobic amino acids is associated with low protein abundance, low protein halflife, and low translation efficiency, progressive enrichment of alanine or valine is associated with complete opposite trends in protein metabolism [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
