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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Structural models of human eEF1A1 and eEF1A2 reveal two distinct surface clusters of sequence variation and potential
Dinesh C Soares1, Paul N Barlow, Helen J Newbery
1Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom. Dinesh.Soares@ed.ac.uk
Plos One
|July 29, 2009
Summary
Comparative 3-D models reveal distinct surface features and potential phosphorylation differences between human translation elongation factor 1 alpha-1 (eEF1A1) and eEF1A2, explaining their varied functions beyond protein synthesis.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Human translation elongation factor 1 alpha-1 (eEF1A1) and eEF1A2 share high sequence identity but exhibit distinct functional profiles.
- These differences may stem from cell-type specific requirements and roles beyond tRNA delivery.
Purpose of the Study:
- To investigate the structural basis for functional divergence between eEF1A1 and eEF1A2.
- To identify key amino acid residues and regions responsible for differential protein functions.
Main Methods:
- Comparative three-dimensional (3-D) modeling of eEF1A1 and eEF1A2 based on yeast eEF1A crystal structure.
- Analysis of spatial location, surface electrostatic, and lipophilic properties of variant amino acid residues.
- Sequence-based predictions for phosphorylation sites.
Main Results:
- Identified two distinct sub-clusters of variant surface-exposed residues on one face of the proteins.
- Found no significant structural impact from variations in buried residues.
- Predicted differences in phosphorylation sites that may explain functional divergence.
- Variant residues are located near sites involved in binding GTP/GDP, eEF1Balpha, and aminoacyl-tRNA.
Conclusions:
- The 3-D models provide a structural framework for understanding eEF1A1 and eEF1A2 functional differences.
- Identified surface sub-clusters enable targeted mutagenesis to map protein interaction sites.
- Predicted variant-specific phosphorylation sites offer avenues for experimental verification.
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