Abstract
Corneal dystrophies (CDs) are a group of inherited bilateral disorders affecting the corneal tissue of the eye. Most of these CDs in the stromal layer of the cornea have been associated with mutations found on the TGFBI gene that codes for a 683-amino acid transforming growth factor induced protein (TGFβIp). These mutations have been found to induce atypical aggregation and progressive accumulation of protein aggregates in the cornea that leads to loss of corneal transparency and hence blindness. At present, 65 distinct pathogenic mutations have been identified in TGFBI that are associated with different clinical phenotypes. More than 80% of these missense mutations occur in the 4th FAS (fasciclin-like) 1 domain. Current treatment includes surgical intervention, which often involves high recurrence rates. Hence, it is imperative to examine the properties of the TGFβIp and the pathogenic mutant proteins to understand the pathology of the disease mechanism and to develop potent therapeutics. Here, we report the recombinant expression, purification, characterization and the effect of four clinically significant pathogenic TGFβIp mutants - R555W, H572R, A620D, and H626R on the biophysical properties of the wild type (WT) 4th FAS1 d...Continue Reading
References
May 5, 1986·Journal of Molecular Biology·F W Studier, B A Moffatt
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·A N BullockA R Fersht
Feb 7, 2001·The Journal of Biological Chemistry·E KorvatskaD F Schorderet
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·M Ramirez-AlvaradoL Regan
Oct 3, 2000·Proteins·C N Pace, K L Shaw
Jul 5, 2003·Analytical Biochemistry·Vincent RaussensErik Goormaghtigh
Dec 22, 2004·The Journal of Biological Chemistry·Giulia CalloniFabrizio Chiti
May 10, 2006·Human Mutation·Chitra Kannabiran, Gordon K Klintworth
Oct 3, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Ji-Ho YooHyun-Soo Cho
Feb 23, 2008·Experimental Eye Research·Kasper RunagerGordon K Klintworth
Feb 25, 2009·Orphanet Journal of Rare Diseases·Gordon K Klintworth
Apr 8, 2009·Cornea·Jayne S WeissGordon K Klintworth
Jun 2, 2009·Brain Research Bulletin·Yureeda QaziBalamurali K Ambati
Oct 8, 2009·Brain Research Bulletin·Alexei Surguchev, Andrei Surguchov
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Davin M HendersonJames M Ervasti
Jul 6, 2010·Experimental Eye Research·John R Hassell, David E Birk
Citations
Dec 7, 2013·PLoS Biology·Adrien RousseauFabien Alpy
Jun 19, 2013·FEBS Open Bio·Robert G Moody, Mike P Williamson
Mar 11, 2016·International Ophthalmology·Sabine FojaClaudia Gruenauer-Kloevekorn
Aug 16, 2015·Biomolecular NMR Assignments·Natalia V KulminskayaFrans A A Mulder
Apr 1, 2016·Scientific Reports·Elavazhagan MuruganJodhbir S Mehta
Jan 6, 2015·The Ocular Surface·R LakshminarayananJodhbir S Mehta
Mar 7, 2020·Scientific Reports·Anandalakshmi VenkatramanJodhbir S Mehta
Mar 28, 2019·Journal of Ophthalmology·Qin XiangHao Deng
Jul 9, 2020·Journal of Advanced Research·Anandalakshmi VenkatramanJodhbir Singh Mehta
Nov 16, 2017·Biochemistry·Nadia Sukusu NielsenJan J Enghild