Table of Contents
Journal of Biophysics
Volume 2013 (2013), Article ID 525231, 11 pages
Research Article

Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques

1Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
2Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
3Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
5Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA

Received 28 November 2012; Accepted 7 May 2013

Academic Editor: P. Bryant Chase

Copyright © 2013 Meixiang Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.