Related Experiment Video
Updated: Jul 23, 2026
14:55
Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Correlation between 2H NMR side-chain order parameters and sequence conservation in globular proteins
Anthony Mittermaier1, Alan R Davidson, Lewis E Kay
1Protein Engineering Network Centres of Excellence, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Journal of the American Chemical Society
|September 17, 2004
Summary
Protein sequence preference, not just solvent accessibility, influences side-chain mobility in proteins. Conserved structural features, like hydrogen bonds, appear to govern internal protein dynamics.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Side-chain dynamics are crucial for protein function.
- Hydrophobic burial is a known factor influencing protein internal dynamics.
- Understanding factors governing protein internal dynamics is key to protein engineering and drug design.
Purpose of the Study:
- To investigate the relationship between sequence preference, solvent accessibility, and side-chain dynamics in proteins.
- To identify conserved structural features that dictate protein internal dynamics beyond hydrophobic interactions.
Main Methods:
- Collected side-chain 2H NMR relaxation data for the SH3 domain of Fyn tyrosine kinase.
- Analyzed relaxation data with respect to sequence preference and per-residue solvent accessibility.
- Compared findings across six additional protein systems.
Main Results:
- Residues with higher sequence preference exhibited reduced mobility compared to average.
- Sequence preference showed a stronger correlation with mobility than solvent accessibility.
- This trend was consistent across most proteins studied.
- Identified side-chain hydrogen bonding and specific secondary structures as potential determinants of internal dynamics.
Conclusions:
- Sequence preference is a significant determinant of side-chain mobility in proteins.
- Conserved structural features, including hydrogen bonding and secondary structures, play a vital role in governing protein internal dynamics.
- These findings offer new insights into the principles of protein structure-function relationships.
More Related Videos
Related Concept Videos
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...
01:49Conserved 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...
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
02:26Conservation of Protein Domains
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...
01:49Conserved 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...
01:03¹H NMR Chemical Shift Equivalence: Homotopic and Heterotopic Protons
Protons in identical electronic environments within a molecule are chemically equivalent and have the same chemical shift. The replacement test is a useful tool to identify chemical equivalence and predict NMR spectra. A substituent replaces each of the protons being examined and the resulting molecules are compared. If the same molecule is obtained, the protons are equivalent or homotopic. Replacement of any hydrogens in ethane by chlorine yields chloroethane because all six protons are...