Related Experiment Video
Updated: Jul 9, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Conserved spatial patterns across the protein kinase family
Lynn F Ten Eyck1, Susan S Taylor, Alexandr P Kornev
1Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. lynn.teneyck@ucd.ie
Biochimica Et Biophysica Acta
|December 11, 2007
Summary
Protein kinases, crucial for cell signaling, possess a unique "spine" structure in their active form. This spine, essential for kinase function, is dynamically disassembled upon inactivation and undetectable by traditional methods.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Protein kinases are essential enzymes regulating vital cellular processes like signal transduction, metabolism, and cell growth.
- Precise control of protein kinase activity is critical, necessitating sophisticated mechanisms for signal and substrate recognition.
- Comparing protein surfaces is challenging due to sequence and conformational variability.
Purpose of the Study:
- To compare serine/threonine and tyrosine kinases using a novel protein surface comparison method.
- To identify conserved structural features related to protein kinase activity and regulation.
- To investigate the structural basis of protein kinase activation and inactivation.
Main Methods:
- Application of a recently developed protein surface comparison technique.
- Analysis of diverse serine/threonine and tyrosine kinase structures.
- Identification and characterization of conserved structural elements within the kinase active site.
Main Results:
- Discovery of a conserved structural feature, termed the "spine", connecting two hydrophobic cores in active protein kinases.
- Demonstration that the "spine" is unique to the active conformation and disassembles during inactivation.
- Confirmation that the "spine" residues do not form traditional sequence or 3D motifs, making them undetectable by other methods.
Conclusions:
- The "spine" represents a novel, conformation-specific structural element critical for protein kinase activity.
- This finding provides new insights into the dynamic regulation of protein kinase function.
- The developed surface comparison method offers a powerful tool for identifying functionally relevant, non-traditional structural motifs in proteins.
Related Concept Videos
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...