MCPT, PEH, and LACG are recipients of CONACYT postdoctoral, doctoral and master's fellowships, respectively. EFA was recipient of ICYTDF-299 postdoctoral fellowship.
Structural and thermodynamic folding characterization of triosephosphate isomerases from Trichomonas vaginalis reveals the role of destabilizing mutations following gene duplication
Article first published online: 31 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 82, Issue 1, pages 22–33, January 2014
How to Cite
Lara-González, S., Estrella-Hernández, P., Ochoa-Leyva, A., del Carmen Portillo-Téllez, M., Caro-Gómez, L. A., Figueroa-Angulo, E. E., Salgado-Lugo, H., Miranda Ozuna, J. F. T., Ortega-López, J., Arroyo, R., Brieba, L. G. and Benítez-Cardoza, C. G. (2014), Structural and thermodynamic folding characterization of triosephosphate isomerases from Trichomonas vaginalis reveals the role of destabilizing mutations following gene duplication. Proteins, 82: 22–33. doi: 10.1002/prot.24333
- Issue published online: 11 DEC 2013
- Article first published online: 31 AUG 2013
- Accepted manuscript online: 4 JUN 2013 02:00AM EST
- Manuscript Accepted: 3 MAY 2013
- Manuscript Revised: 1 MAY 2013
- Manuscript Received: 7 OCT 2012
- ICYTDF project “PICSA 10-19, 6968-Diseño racional, síntesis y evaluación de fármacos contra la infección de transmisión sexual tricomonosis” (to CGBC)
- ICYTDF-299 and ICYTDF-219 (to RA)
- CONACYT. Grant Number: CB-2009-128647 (to LGB), CB-2008-101229, and SIP–IPN 20120190 and 20130366 (to CGBC), CB-153093, and Salud 162123 (to RA)
- TIM barrel;
- crystal structures;
- thermodynamic analysis of the unfolding;
- monomer association;
- moonlighting protein
We report the structures and thermodynamic analysis of the unfolding of two triosephosphate isomerases (TvTIM1 and TvTIM2) from Trichomonas vaginalis. Both isoforms differ by the character of four amino acids: E/Q 18, I/V 24, I/V 45, and P/A 239. Despite the high sequence and structural similarities between both isoforms, they display substantial differences in their stabilities. TvTIM1 (E18, I24, I45, and P239) is more stable and less dissociable than TvTIM2 (Q18, V24, V45, and A239). We postulate that the identities of residues 24 and 45 are responsible for the differences in monomer stability and dimer dissociability, respectively. The structural difference between both amino acids is one methyl group. In TvTIMs, residue 24 is involved in packing α-helix 1 against α-helix 2 of each monomer and residue 45 is located at the center of the dimer interface forming a “ball and socket” interplay with a hydrophobic cavity. The mutation of valine at position 45 for an alanine in TvTIM2 produces a protein that migrates as a monomer by gel filtration. A comparison with known TIM structures indicates that this kind of interplay is a conserved feature that stabilizes dimeric TIM structures. In addition, TvTIMs are located in the cytoplasm and in the membrane. As TvTIM2 is an easily dissociable dimer, the dual localization of TvTIMs may be related to the acquisition of a moonlighting activity of monomeric TvTIM2. To our knowledge, this is the simplest example of how a single amino acid substitution can provide alternative function to a TIM barrel protein. Proteins 2014; 82:22–33. © 2013 Wiley Periodicals, Inc.