pH Induced Conformational Transitions in the Transforming Growth Factor β-Induced Protein (TGFβIp) Associated Corneal Dystrophy Mutants
作者： Elavazhagan Murugan , Anandalakshmi Venkatraman , Zhou Lei , Victoria Mouvet , Rayne Rui Yi Lim
DOI: 10.1038/SREP23836
关键词:
摘要: Most stromal corneal dystrophies are associated with aggregation and deposition of the mutated transforming growth factor-β induced protein (TGFβIp). The 4th_FAS1 domain TGFβIp harbors ~80% mutations that forms amyloidogenic non-amyloidogenic aggregates. To understand mechanism differences between phenotypes, we expressed domains carrying R555W (non-amyloidogenic) H572R (amyloidogenic) along wild-type (WT). was more susceptible to acidic pH compared displayed varying chemical stabilities decreasing pH. Thermal denaturation studies at showed while WT did not undergo any conformational transition, mutants exhibited a clear pH-dependent irreversible conversion from αβ conformation β-sheet oligomers. β-oligomers both were stable physiological temperature Electron microscopy dynamic light scattering larger R555W. cytotoxic primary human fibroblast (pHCSF) cells. exhibit variations in their morphologies, sizes, thermal stabilities, patterns cytotoxicities.
nature.com
core.ac.uk
harvard.edu
sci-hub.se 参考文章(59)
The IC3D Classification of the Corneal Dystrophies Cornea. ,vol. 27, ,(2008) , 10.1097/ICO.0B013E31817780FB
Thomas E. Creighton, Protein structure : a practical approach IRL Press at Oxford University Press. ,(1990)
Clair-Florent Schmitt-Bernard, Alain Chavanieu, Gudrun Herrada, Guy Subra, Bernard Arnaud, Jacques G. Demaille, Bernard Calas, Ángel Argilés, BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro. FEBS Journal. ,vol. 269, pp. 5149- 5156 ,(2002) , 10.1046/J.1432-1033.2002.03205.X
Mauricio Moraga, Luisa Herrera, Pablo Romero, Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3) Molecular Vision. ,vol. 16, pp. 1601- 1609 ,(2010)
Francis L Munier, Beatrice E Frueh, Philippe Othenin-Girard, Sylvie Uffer, Pascal Cousin, Ming X Wang, Elise Héon, Graeme CM Black, Maria A Blasi, Emilio Balestrazzi, Birgit Lorenz, Rafael Escoto, Rafael Barraquer, Maria Hoeltzenbein, Balder Gloor, Maurizio Fossarello, Arun D Singh, Yvan Arsenijevic, Léonidas Zografos, Daniel F Schorderet, None, BIGH3 mutation spectrum in corneal dystrophies. Investigative Ophthalmology & Visual Science. ,vol. 43, pp. 949- 954 ,(2002)
Ching Yuan, Heather L. Berscheit, Andrew J.W. Huang, Identification of an amyloidogenic region on keratoepithelin via synthetic peptides. FEBS Letters. ,vol. 581, pp. 241- 247 ,(2007) , 10.1016/J.FEBSLET.2006.12.019
Bong-Yoon Kim, James A. Olzmann, Seung-il Choi, So Yeon Ahn, Tae-im Kim, Hyun-Soo Cho, Hwal Suh, Eung Kweon Kim, Corneal dystrophy-associated R124H mutation disrupts TGFBI interaction with Periostin and causes mislocalization to the lysosome. Journal of Biological Chemistry. ,vol. 284, pp. 19580- 19591 ,(2009) , 10.1074/JBC.M109.013607
R. Lakshminarayanan, Shyam S. Chaurasia, Elavazhagan Murugan, Anandalakshmi Venkatraman, Shu-Ming Chai, Eranga N. Vithana, Roger W. Beuerman, Jodhbir S. Mehta, Biochemical properties and aggregation propensity of transforming growth factor-induced protein (TGFBIp) and the amyloid forming mutants. Ocular Surface. ,vol. 13, pp. 9- 25 ,(2015) , 10.1016/J.JTOS.2014.04.003
Fabrizio Chiti, Massimo Stefani, Niccolò Taddei, Giampietro Ramponi, Christopher M. Dobson, Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature. ,vol. 424, pp. 805- 808 ,(2003) , 10.1038/NATURE01891
C. M. Pfefferkorn, R. P. McGlinchey, J. C. Lee, Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17 Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 21447- 21452 ,(2010) , 10.1073/PNAS.1006424107