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Structure-function analysis of CD14 as a soluble receptor for lipopolysaccharide
S Viriyakosol1, J C Mathison, P S Tobias
1Department of Pathology, University of California San Diego School of Medicine, the Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA.
The Journal of Biological Chemistry
|February 1, 2000
Summary
Soluble and membrane CD14 show distinct structural requirements for lipopolysaccharide (LPS) binding and cell activation. Mutations affecting LPS receptor function differently impact soluble CD14 compared to membrane-bound forms.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD14 is a protein involved in cellular activation by lipopolysaccharide (LPS).
- Both membrane-bound and soluble forms of CD14 exist, with differing structures.
- Previous studies identified LPS binding and cell activation functions of CD14 deletion mutants.
Purpose of the Study:
- To investigate the functional impact of CD14 mutations on soluble CD14.
- To compare the LPS binding and receptor functions of soluble CD14 mutants with membrane CD14 mutants.
Main Methods:
- Studied five deletion mutants of CD14.
- Assessed LPS binding affinity for both membrane and soluble CD14 forms.
- Evaluated the cellular activation function of soluble CD14 mutants.
Main Results:
- Some mutations abrogated LPS binding in membrane CD14 but not soluble CD14.
- Certain soluble CD14 mutants exhibited higher LPS binding affinity than wild-type CD14.
- All five deletions ablated soluble CD14 LPS receptor function, while only two affected membrane CD14 function.
Conclusions:
- Soluble and membrane CD14 possess distinct structural determinants for LPS receptor function.
- The functional differences highlight the unique roles of soluble and membrane CD14 in immune responses.