Research article

Molecular dynamics simulation of human LOX-1 provides an explanation for the lack of OxLDL binding to the Trp150Ala mutant

Mattia Falconi¹ , Silvia Biocca² , Giuseppe Novelli³ and Alessandro Desideri¹

¹  Department of Biology and Center of Biostatistics and Bioinformatics, University of Rome "Tor Vergata", Via della Ricerca Scientifica, Rome, Italy, 00133

²  Department of Neuroscience and Center of Biostatistics and Bioinformatics, University of Rome "Tor Vergata", Via di Tor Vergata, 135, Rome, Italy, 00133

³  Department of Biopathology and Diagnostic Imaging and Center of Biostatistics and Bioinformatics, University of Rome "Tor Vergata", Azienda Ospedaliera Universitaria, Policlinico Tor Vergata Viale Oxford 81, Rome, Italy, 00133 and Fondazione Livio Patrizi, Rome, Italy

author email corresponding author email

BMC Structural Biology 2007, 7:73doi:10.1186/1472-6807-7-73

Published:	7 November 2007

Abstract

Background

Dimeric lectin-like oxidized low-density lipoprotein receptor-1 LOX-1 is the target receptor for oxidized low density lipoprotein in endothelial cells. In vivo assays revealed that in LOX-1 the basic spine arginine residues are important for binding, which is lost upon mutation of Trp150 with alanine. Molecular dynamics simulations of the wild-type LOX-1 and of the Trp150Ala mutant C-type lectin-like domains, have been carried out to gain insight into the severe inactivating effect.

Results

The mutation does not alter the dimer stability, but a different dynamical behaviour differentiates the two proteins. As described by the residues fluctuation, the dynamic cross correlation map and the principal component analysis in the wild-type the two monomers display a symmetrical motion that is not observed in the mutant.

Conclusion

The symmetrical motion of monomers is completely damped by the structural rearrangement caused by the Trp150Ala mutation. An improper dynamical coupling of the monomers and different fluctuations of the basic spine residues are observed, with a consequent altered binding affinity.