Functional Analysis and Molecular Dynamics Simulation of LOX-1 K167N Polymorphism Reveal Alteration of Receptor Activity
2009

Effects of LOX-1 K167N Mutation on Receptor Activity

publication 10 minutes Evidence: moderate

Author Information

Author(s): Biocca Silvia, Falconi Mattia, Filesi Ilaria, Baldini Francesco, Vecchione Lucia, Mango Ruggiero, Romeo Francesco, Federici Giorgio, Desideri Alessandro, Novelli Giuseppe

Primary Institution: Department of Neuroscience, University of Tor Vergata, Rome, Italy

Hypothesis

Does the c.501G>C polymorphism change the binding affinity of LOX-1 receptor altering its function?

Conclusion

The K167N mutation in the LOX-1 receptor reduces its ability to bind oxidized low-density lipoprotein (ox-LDL) and impairs its signaling activity.

Supporting Evidence

  • The K167N mutation reduces ox-LDL binding and uptake.
  • The mutation impairs ERK 1/2 activation in response to ox-LDL.
  • Human macrophages with the K167N mutation show decreased LOX-1 induction upon ox-LDL treatment.

Takeaway

A change in a specific part of a protein can make it less effective at grabbing onto bad cholesterol, which might lead to heart problems.

Methodology

The study involved expressing wild-type and mutated LOX-1 in cell lines and analyzing their binding and signaling activities.

Limitations

The study does not confirm the effects of the mutation in vivo or in a larger population.

Participant Demographics

The study involved human macrophages derived from volunteers with different genotypes.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0004648

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