TY - JOUR
T1 - Molecular dynamics simulation of human LOX-1 provides an explanation for the lack of OxLDL binding to the Trp150Ala mutant
AU - Falconi, Mattia
AU - Biocca, Silvia
AU - Novelli, Giuseppe
AU - Desideri, Alessandro
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
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U2 - 10.1186/1472-6807-7-73
DO - 10.1186/1472-6807-7-73
M3 - Article
C2 - 17988382
AN - SCOPUS:38149137291
VL - 7
JO - BMC Structural Biology
JF - BMC Structural Biology
SN - 1472-6807
M1 - 73
ER -