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HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal
Roland K Strong1, Margaret A Holmes, Pingwei Li
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. rstrong@fhcrc.org
The Journal of Biological Chemistry
|November 2, 2002
Summary
Human Leukocyte Antigen-E (HLA-E) alleles show functional differences due to a single amino acid change, impacting cell surface levels and potentially explaining balancing selection in populations.
Area of Science:
- Immunogenetics
- Molecular biology
- Protein biochemistry
Background:
- Human Leukocyte Antigen-E (HLA-E) allelic polymorphism suggests functional differences between alleles.
- Two major HLA-E alleles, E(R) (arginine at position 107) and E(G) (glycine at position 107), differ by a single amino acid.
Purpose of the Study:
- To investigate the physical and biochemical differences between HLA-E*0101 (E(R)) and HLA-E*0103 (E(G)) alleles.
- To elucidate the functional consequences of the single amino acid substitution at position 107.
Main Methods:
- Comparison of protein expression levels and cell surface levels.
- Analysis of peptide affinity, complex stability, and three-dimensional structure using crystallography.
- Thermal stability assays.
Main Results:
- Steady-state protein levels were similar, but cell surface levels differed between E(R) and E(G) alleles.
- No significant structural differences were observed in HLA-E regardless of peptide binding or allelic substitution.
- Differences in thermal stability correlated with peptide-binding affinity and cell surface expression levels.
Conclusions:
- The single amino acid substitution between HLA-E alleles influences thermal stability and peptide-binding affinity.
- These biochemical differences explain the observed variations in cell surface expression levels.
- The findings provide a molecular basis for the balancing selection observed at the HLA-E locus.