CPAfold

CPAfold annotates topology and generates structural models of CPA/AT transporters to elucidate their structural variations and evolutionary transitions.

Key Features:

• Integrated topology annotation: Employs an integrated topology annotation method to define transmembrane topology across CPA/AT families.
• Structural modeling: Generates structural models for all families of CPA/AT transporters.
• Domain annotation: Identifies scaffold and core domains and highlights the core-domain non-canonical helices (broken or reentrant).
• Fold-type classification: Classifies CPA/AT transporters into four fold-types: CPA-Broken, CPA-Reentrant, BART, and Reentrant-Helix-Reentrant.
• Topological transition detection: Detects topological transitions including broken↔reentrant helix changes, loop→reentrant helix conversions, complete orientation shifts, and changes in the number of scaffold helices.
• Evolutionary inference: Associates observed structural and topological changes with gene duplication and shuffling events.
• Per-family annotations: Produces detailed topology information and structural models for each transporter family.

Scientific Applications:

• Membrane protein structure–function studies: Comparative structural and topology annotations support analysis of CPA/AT transporter mechanism and function.
• Evolutionary biology: Characterizes evolutionary transitions in transporter structure and topology linked to gene duplication and shuffling.
• Fold discovery and classification: Enables identification and classification of novel fold-types such as Reentrant-Helix-Reentrant within CPA/AT families.

Methodology:

Applies an integrated topology annotation method to generate structural models, classify families into four fold-types, and identify topological transitions.