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Structure-based classification of 45 FK506-binding proteins
J A Somarelli1, S Y Lee, J Skolnick
1Department of Biological Sciences, OE304, Florida International University, Miami, Florida 33199, USA.
Proteins
|January 25, 2008
Summary
FK506-binding proteins (FKBPs) are crucial chaperones with diverse roles. Computational modeling revealed evolutionary changes and potential new functions, including drug interactions and nucleic acid binding.
Area of Science:
- Biochemistry
- Structural Biology
- Evolutionary Biology
Background:
- FK506-binding proteins (FKBPs) are conserved chaperones involved in numerous cellular processes.
- Their functions are linked to specific tertiary structures and domains.
- Understanding FKBP structure-function relationships is key to deciphering their roles.
Purpose of the Study:
- To predict and analyze the tertiary structures of a diverse set of FKBP proteins.
- To classify FKBP homologs based on structural predictions.
- To investigate potential evolutionary modifications and novel functional interactions of FKBPs.
Main Methods:
- Tertiary structure prediction using the Threading/ASSEmbly/Refinement (TASSER) approach for 45 FKBP proteins across 23 species.
- Comparison of predicted models with existing FKBP solution structures.
- Identification of homologous protein groups and evolutionary sequence modifications.
- Molecular docking simulations to explore drug binding and protein-protein interactions.
Main Results:
- Successfully predicted tertiary structures for 45 FKBP proteins, enabling homology-based classification.
- Identified significant evolutionary modifications within the FKBP family, including domain losses, duplications, and motif insertions.
- Docking simulations suggested that extrachain segments influence drug binding affinity.
- Revealed a potential helix-loop-helix (HLH) region in some FKBPs, implicating them in nucleic acid interactions.
Conclusions:
- The structural classification of FKBPs aids in inferring functions of newly identified members.
- FKBP evolution involves substantial structural diversification.
- FKBPs possess uncharacterized regions and domains that influence their interactions with drugs and nucleic acids, expanding their known functional repertoire.
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