[Computer construction and analysis of protein models of mutant fibrillin-1 gene in Marfan's syndrome].
OBJECTIVE
Fibrillin-1, the major constituent of extracellular microfibrils, plays an important role in the molecular pathogenesis of Marfan syndrome (MFS, #54700). The aim of this study was to analyze protein models of the mutation of the fibrillin-1 (FBN1) gene on Arg545Cys and Arg1530Cys which have been reported to cause predominant ectopia lentis in Chinese patients.


METHODS
We constructed and analyzed the protein models of the mutant FBN1 gene on Arg545Cys and Arg1530Cys. Fibrillin-1 protein structures were predicted by SWISS-MODEL. Models were viewed in Swiss-Pdb Viewer.


RESULTS
Computer construction and analysis of protein models of the mutant FBN1 gene revealed that the mutant Arg545Cys FBN1 protein had various changes on protein's secondary structure with an absence of a helix, decreased hydrogen bond distance, different protein surface solvent-accessibility and decreased negative electrostatic potential. The mutant Arg1530Cys FBN1 showed lost of hydrogen bonds, different protein surface solvent-accessibility and increased negative electrostatic potential.


CONCLUSIONS
Protein models of the mutant FBN1 gene shows significant alterations on the protein's secondary structure based on computer construction and analysis technology. This study provides further evidence for the important effect of the mutant FBN1 on the pathogenesis of human ectopia lentis.
Shentu
Xing-chao
XC
Eye Center, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, China.
Tang
Xia-jing
XJ
Ye
Pan-pan
PP
Jin
Chong-fei
CF
Wang
Wei
W
Yao
Ke
K
D003198:Computer Simulation; D004479:Ectopia Lentis / Q000235:genetics*; D005091:Exons; D000071838:Fibrillin-1; D000071837:Fibrillins; D005796:Genes; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics*; D020894:Microfibrils; D008840:Microfilament Proteins / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D017433:Protein Structure, Secondary; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines