Rapid Evolution Exposes the Boundaries of Domain Structure and Function in Natively Unfolded FG Nucleoporins
| Autor: | Michael Rexach, Daniel P. Denning |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Protein Folding
Phenylalanine Amino Acid Motifs Molecular Sequence Data Protein domain Saccharomyces cerevisiae Glycine Biology Biochemistry Analytical Chemistry Conserved sequence Evolution Molecular Animals Humans Amino Acid Sequence Nuclear pore Molecular Biology Peptide sequence Conserved Sequence Karyopherin chemistry.chemical_classification Sequence Homology Amino Acid biology.organism_classification Protein Structure Tertiary Cell biology Nuclear Pore Complex Proteins chemistry Nuclear Pore Protein folding Nucleoporin |
| Zdroj: | Molecular & Cellular Proteomics. 6:272-282 |
| ISSN: | 1535-9476 |
| DOI: | 10.1074/mcp.m600309-mcp200 |
| Popis: | Nucleoporins with phenylalanine-glycine repeats (FG Nups) function at the nuclear pore complex (NPC) to facilitate nucleocytoplasmic transport. In Saccharomyces cerevisiae, each FG Nup contains a large natively unfolded domain that is punctuated by FG repeats. These FG repeats are surrounded by hydrophilic amino acids (AAs) common to disordered protein domains. Here we show that the FG domain of Nups from human, fly, worm, and other yeast species is also enriched in these disorder-associated AAs, indicating that structural disorder is a conserved feature of FG Nups and likely serves an important role in NPC function. Despite the conservation of AA composition, FG Nup sequences from different species show extensive divergence. A comparison of the AA substitution rates of proteins with syntenic orthologs in four Saccharomyces species revealed that FG Nups have evolved at twice the rate of average yeast proteins with most substitutions occurring in sequences between FG repeats. The rapid evolution of FG Nups is poorly explained by parameters known to influence AA substitution rate, such as protein expression level, interactivity, and essentiality; instead their rapid evolution may reflect an intrinsic permissiveness of natively unfolded structures to AA substitutions. The overall lack of AA sequence conservation in FG Nups is sharply contrasted by discrete stretches of conserved sequences. These conserved sequences highlight known karyopherin and nucleoporin binding sites as well as other uncharacterized sites that may have important structural and functional properties. |
| Databáze: | OpenAIRE |
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