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Sequence-structure signals of 3D domain swapping in proteins
Yves Dehouck1, Christophe Biot, Dimitri Gilis
1Ingénierie Biomoléculaire, Université Libre de Bruxelles, CP 165/64, 50 Avenue Roosevelt, B-1050 Bruxelles, Belgium. ydehouck@ulb.ac.be
Journal of Molecular Biology
|July 16, 2003
Summary
This study identifies sequence features that predict protein three-dimensional domain swapping, a process implicated in protein evolution and disease. These findings aid in understanding and potentially controlling protein structure dynamics.
Area of Science:
- Protein structure and dynamics
- Computational biology
- Molecular evolution
Background:
- Three-dimensional domain swapping is a protein oligomerization mechanism.
- It impacts protein evolution, function, and disease.
- Understanding its sequence determinants is crucial.
Purpose of the Study:
- To identify sequence-based predictors of three-dimensional domain swapping.
- To investigate the role of sequence in protein structural stability and conformational preferences.
- To explore the influence of cation-pi interactions on domain swapping interfaces.
Main Methods:
- Utilized algorithms for predicting protein structure and stability from sequence.
- Employed database-derived potentials for stability assessments.
- Analyzed sequence regions for native vs. non-native conformational preferences.
Main Results:
- Detected sequence regions suboptimal for native stability or favoring non-native states in domain-swapping proteins.
- Identified these critical regions often influence the swapping process kinetically or thermodynamically.
- Observed frequent cation-pi interactions stabilizing domain-swapping interfaces and hinge regions.
Conclusions:
- Sequence analysis can reveal propensity for three-dimensional domain swapping.
- Specific sequence characteristics and interactions like cation-pi bonds modulate protein structural dynamics.
- Proposed mutations for experimental validation of in silico predictions.