ArticleScientific reports2011
Stability of domain structures in multi-domain proteins.
Article in Scientific reports, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
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- Colorectal cancer-associated PCBP1 mutations disrupt protein stability in a dominant negative manner.bioRxiv : the preprint server for biology · 2025Article
- Fibrinogen-binding M-related proteins facilitate the recruitment of plasminogen by Streptococcus pyogenes.Protein science : a publication of the Protein Society · 2025Article
- Identification of 121 variants of honey bee Vitellogenin protein sequences with structural differences at functional sites.Protein science : a publication of the Protein Society · 2022Article
- Structural and dynamic studies of the peptidase domain from Clostridium thermocellum PCAT1.Protein science : a publication of the Protein Society · 2022Article
- No evidence for widespread positive selection on double substitutions within codons in primates and yeasts.Frontiers in genetics · 2022Article
- Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance.Journal of the American Chemical Society · 2021Article
- PPIDomainMiner: Inferring domain-domain interactions from multiple sources of protein-protein interactions.PLoS computational biology · 2021Article
- Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies.International journal of molecular sciences · 2021Article
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- Biophysical and Dynamic Characterization of Fine-Tuned Binding of the Human Respiratory Syncytial Virus M2-1 Core Domain to Long RNAs.Journal of virology · 2020Article
- Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase.eLife · 2020Article
- MetaGeneHunt for protein domain annotation in short-read metagenomes.Scientific reports · 2020Article
- Functional Disassociation Between the Protein Domains of MSMEG_4305 ofFrontiers in microbiology · 2020Article
- Energetic dependencies dictate folding mechanism in a complex protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Directed evolution of the metalloproteinase inhibitor TIMP-1 reveals that its N- and C-terminal domains cooperate in matrix metalloproteinase recognition.The Journal of biological chemistry · 2019Article
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR.
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