Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques
Joint Authors
Sutton, R. Bryan
Qian, Feng
Xu, Meixiang
Bujalowski, Paul J.
Ma, Liang
Oberhauser, Andres F.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-26
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Polycystin-1 is a large transmembrane protein, which, when mutated, causes autosomal dominant polycystic kidney disease, one of the most common life-threatening genetic diseases that is a leading cause of kidney failure.
The REJ (receptor for egg lelly) module is a major component of PC1 ectodomain that extends to about 1000 amino acids.
Many missense disease-causing mutations map to this module; however, very little is known about the structure or function of this region.
We used a combination of homology molecular modeling, protein engineering, steered molecular dynamics (SMD) simulations, and single-molecule force spectroscopy (SMFS) to analyze the conformation and mechanical stability of the first ~420 amino acids of REJ.
Homology molecular modeling analysis revealed that this region may contain structural elements that have an FNIII-like structure, which we named REJd1, REJd2, REJd3, and REJd4.
We found that REJd1 has a higher mechanical stability than REJd2 (~190 pN and 60 pN, resp.).
Our data suggest that the putative domains REJd3 and REJd4 likely do not form mechanically stable folds.
Our experimental approach opens a new way to systematically study the effects of disease-causing mutations on the structure and mechanical properties of the REJ module of PC1.
American Psychological Association (APA)
Xu, Meixiang& Ma, Liang& Bujalowski, Paul J.& Qian, Feng& Sutton, R. Bryan& Oberhauser, Andres F.. 2013. Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques. Journal of Biophysics،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-478618
Modern Language Association (MLA)
Xu, Meixiang…[et al.]. Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques. Journal of Biophysics No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-478618
American Medical Association (AMA)
Xu, Meixiang& Ma, Liang& Bujalowski, Paul J.& Qian, Feng& Sutton, R. Bryan& Oberhauser, Andres F.. Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques. Journal of Biophysics. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-478618
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-478618