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Updated: May 8, 2026
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Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Consequences of domain insertion on sequence-structure divergence in a superfold.
Chetanya Pandya1, Shoshana Brown, Ursula Pieper
1Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA.
Summary
Protein fold evolution, driven by domain insertions, shows core domain robustness to mutations. However, cap domain type influences core domain similarity, indicating interplay and differential divergence.
Area of Science:
- Protein structure and evolution
- Structural bioinformatics
- Molecular evolution
Background:
- Protein structures, though vast, derive from a finite set of folds.
- Functional evolution often involves elaborating existing protein scaffolds through domain insertions.
- Understanding how protein folds diversify via domain insertions is crucial.
Purpose of the Study:
- To investigate the impact of cap-domain insertion on the sequence and structure divergence of the core domain within the haloalkanoic dehalogenase superfamily.
- To uncover evolutionary principles governing protein fold diversification through domain insertions.
Main Methods:
- Quantitative analysis of a dataset comprising 154 core-domain-only and cap-domain-only protein structures.
- Comparative analysis of sequence and structural divergence between core and cap domains.
Main Results:
- The relationship between sequence and structure divergence in the core domain is monotonic and independent of the cap-domain insert type, highlighting the Rossmann fold's robustness.
- Core domains associated with the same cap type exhibit higher sequence and structural similarity, suggesting functional interplay.
- Structural variation is localized to alpha-helices adjacent to the central beta-sheet, not the domain-domain interface.
Conclusions:
- Protein folds can diverge differentially when associated with accessory domains, a phenomenon potentially applicable to other multidomain protein superfamilies.
- Intramolecular coevolution influences how protein folds adapt and diversify in response to domain insertions.
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