Tighter Ligand Binding Can Compensate for Impaired Stability of an RNA-Binding Protein
dc.contributor.author | Wallis, C.P. | |
dc.contributor.author | Richman, T.R. | |
dc.contributor.author | Filipovska, A. | |
dc.contributor.author | Rackham, Oliver | |
dc.date.accessioned | 2023-04-18T07:49:31Z | |
dc.date.available | 2023-04-18T07:49:31Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Wallis, C.P. and Richman, T.R. and Filipovska, A. and Rackham, O. 2018. Tighter Ligand Binding Can Compensate for Impaired Stability of an RNA-Binding Protein. ACS Chemical Biology. 13 (6): pp. 1499-1505. | |
dc.identifier.uri | http://hdl.handle.net/20.500.11937/91509 | |
dc.identifier.doi | 10.1021/acschembio.8b00424 | |
dc.description.abstract |
It has been widely shown that ligand-binding residues, by virtue of their orientation, charge, and solvent exposure, often have a net destabilizing effect on proteins that is offset by stability conferring residues elsewhere in the protein. This structure-function trade-off can constrain possible adaptive evolutionary changes of function and may hamper protein engineering efforts to design proteins with new functions. Here, we present evidence from a large randomized mutant library screen that, in the case of PUF RNA-binding proteins, this structural relationship may be inverted and that active-site mutations that increase protein activity are also able to compensate for impaired stability. We show that certain mutations in RNA-protein binding residues are not necessarily destabilizing and that increased ligand-binding can rescue an insoluble, unstable PUF protein. We hypothesize that these mutations restabilize the protein via thermodynamic coupling of protein folding and RNA binding. © | |
dc.language | English | |
dc.publisher | AMER CHEMICAL SOC | |
dc.relation.sponsoredby | http://purl.org/au-research/grants/arc/DP140104111 | |
dc.relation.sponsoredby | http://purl.org/au-research/grants/arc/DP170103000 | |
dc.relation.sponsoredby | http://purl.org/au-research/grants/arc/DP180101656 | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | 23S RIBOSOMAL-RNA | |
dc.subject | DELETERIOUS MUTATIONS | |
dc.subject | ANTIBIOTIC-RESISTANCE | |
dc.subject | MODULAR RECOGNITION | |
dc.subject | FUNCTION TRADEOFFS | |
dc.subject | STRUCTURAL BASES | |
dc.subject | FOLDING ACTIVITY | |
dc.subject | NUCLEIC-ACIDS | |
dc.subject | DOMAIN-V | |
dc.subject | EVOLUTION | |
dc.subject | Catalytic Domain | |
dc.subject | Humans | |
dc.subject | Ligands | |
dc.subject | Mutagenesis, Site-Directed | |
dc.subject | Mutation | |
dc.subject | Protein Binding | |
dc.subject | Protein Folding | |
dc.subject | Protein Stability | |
dc.subject | RNA | |
dc.subject | RNA-Binding Proteins | |
dc.subject | Humans | |
dc.subject | RNA-Binding Proteins | |
dc.subject | RNA | |
dc.subject | Ligands | |
dc.subject | Mutagenesis, Site-Directed | |
dc.subject | Catalytic Domain | |
dc.subject | Protein Binding | |
dc.subject | Protein Folding | |
dc.subject | Mutation | |
dc.subject | Protein Stability | |
dc.title | Tighter Ligand Binding Can Compensate for Impaired Stability of an RNA-Binding Protein | |
dc.type | Journal Article | |
dcterms.source.volume | 13 | |
dcterms.source.number | 6 | |
dcterms.source.startPage | 1499 | |
dcterms.source.endPage | 1505 | |
dcterms.source.issn | 1554-8929 | |
dcterms.source.title | ACS Chemical Biology | |
dc.date.updated | 2023-04-18T07:49:29Z | |
curtin.department | Curtin Medical School | |
curtin.accessStatus | Open access | |
curtin.faculty | Faculty of Health Sciences | |
curtin.contributor.orcid | Rackham, Oliver [0000-0002-5301-9624] | |
dcterms.source.eissn | 1554-8937 | |
curtin.repositoryagreement | V3 |