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Abstract:

A clear understanding of the structural foundations underlying protein aggregation is an elusive goal of central biomedical importance. A step toward this aim is exemplified by the β- barrel motif represented by the intestinal fatty acid binding protein (IFABP) and two abridged all-β sheet forms (δ98δ and δ78δ). At odds with the established notion that a perturbation of the native fold should necessarily favor a buildup of intermediate forms with an enhanced tendency to aggregate, the intrinsic stability (δG°H2O) of these proteins does not bear a straightforward correlation with their trifluoroethanol (TFE)-induced aggregation propensity. In view of this fact, we found it more insightful to delve into the connection between structure and stability under sub-aggregating conditions (10% TFE). In the absence of the co-solvent, the abridged variants display a common native-like region decorated with a disordered Cterminal stretch. Upon TFE addition, an increase in secondary structure content is observed, assimilating them to the parent protein. In this sense, TFE perturbs a common native like region while exerting a global compaction effect. Importantly, in all cases, fatty acid binding function is preserved. Interestingly, energetic as well as structural diversity in aqueous solution evolves into a common conformational ensemble more akin in stability. These facts reconcile apparent paradoxical findings related to stability and rates of aggregation. This scenario likely mimics the accrual of aggregation-prone species in the population, an early critical event for the development of fibrillation. © 2017 Angelani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Registro:

Documento: Artículo
Título:Structural coalescence underlies the aggregation propensity of a β-barrel protein motif
Autor:Angelani, C.R.; Caramelo, J.J.; Curto, L.M.; Delfino, J.M.
Filiación:Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Buenos Aires, Argentina
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Fundación Instituto Leloir, Buenos Aires, Argentina
Palabras clave:fatty acid binding protein; trifluoroethanol; urea; fatty acid binding protein; protein aggregate; aqueous solution; Article; beta sheet; carboxy terminal sequence; circular dichroism; correlational study; protein aggregation; protein conformation; protein motif; protein secondary structure; protein stability; protein unfolding; structure analysis; animal; chemistry; metabolism; protein motif; rat; Amino Acid Motifs; Animals; Fatty Acid-Binding Proteins; Protein Aggregates; Protein Stability; Rats; Trifluoroethanol
Año:2017
Volumen:12
Número:2
DOI: http://dx.doi.org/10.1371/journal.pone.0170607
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:trifluoroethanol, 75-89-8; urea, 57-13-6; Fatty Acid-Binding Proteins; Protein Aggregates; Trifluoroethanol
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n2_p_Angelani

Referencias:

  • Cohen, S.I.A., Vendruscolo, M., Dobson, C.M., Knowles, T.P.J., From macroscopic measurements to microscopic mechanisms of protein aggregation (2012) J Mol Biol, 421, pp. 160-171. , PMID 22406275
  • Habchi, J., Arosio, P., Perni, M., Costa, A.R., Yagi-Utsumi, M., Joshi, P., An anti-cancer drug suppresses the primary nucleation reaction that initiates the formation of toxic Aβ aggregates associated with Alzheimer's disease (2015) Sci Adv.
  • Richardson, J.S., Richardson, D.C., Natural beta-sheet proteins use negative design to avoid edge-to-edge aggregation (2002) Proc Natl Acad Sci U S A, 99, pp. 2754-2759. , PMID: 11880627
  • Humphrey, W., Dalke, A., Schulten, K., VMD: Visual molecular dynamics (1996) J Mol Graph, 14, pp. 33-38. , http://www.ncbi.nlm.nih.gov/pubmed/8744570, 27-8 PMID: 8744570
  • Curto, L.M., Caramelo, J.J., Delfino, M., Δ98δ, a functional all-beta-sheet abridged form of intestinal fatty acid binding (2005) Biochemistry, 44, pp. 13847-13857. , PMID: 16229473
  • Curto, L.M., Caramelo, J.J., Franchini, G.R., Delfino, J.M., Δ98Δ, a minimalist model of antiparallel β-sheet proteins based on intestinal fatty acid binding protein (2009) Protein Sci, 18, pp. 735-746. , PMID: 19309727
  • Franchini, G.R., Curto, L.M., Caramelo, J.J., Delfino, J.M., Dissection of a β-barrel motif leads to a functional dimer: The case of the intestinal fatty acid binding protein (2009) Protein Sci, 18, pp. 2592-2602. , PMID 19844951
  • Curto, L.M., Angelani, C.R., Caramelo, J.J., Delfino, J.M., Truncation of a β-barrel scaffold dissociates intrinsic stability from its propensity to aggregation (2012) Biophys J, 103, pp. 1929-1939. , PMID 23199921
  • Angelani, C.R., Curto, L.M., Cabanas, I.S., Caramelo, J.J., Uversky, V.N., Delfino, J.M., Toward a common aggregation mechanism for a β-barrel protein family: Insights derived from a stable dimeric species (2014) Biochim Biophys Acta-Proteins Proteomics, 1844, pp. 1599-1607
  • Arighi, C.N., Rossi, J.P.F.C., Delfino, J.M., Temperature-induced conformational switch in intestinal fatty acid binding protein (IFABP) revealing an alternative mode for ligand binding (2003) Biochemistry, 42, pp. 7539-7551. , PMID: 12809510
  • Schmid, F., Spectral methods of characterizing protein conformation and conformational changes (1989) Protein Structure: A Practical Approach, p. 251. , Creighton TE, editor New York: IRL;
  • Lakowicz, J.R., Principles of Fluorescence Spectroscopy, , 3rd ed. New York Springer Science and Business Media;
  • Fersht, A., (1999) Structure and Mechanisms in Protein Science: A Guide to Enzymes Catalysis and Protein Folding, , New York W. H. Freeman and Company;
  • Bolen, D.W., Santoro, M.M., Unfolding Free Energy Changes Determined by the Linear Extrapolation Method
  • Incorporation of delta G degrees N-U values in a thermodynamic cycle (1988) Biochemistry, 27, pp. 8069-8074. , http://www.ncbi.nlm.nih.gov/pubmed/3233196, PMID: 3233196
  • Hong, D.P., Hoshino, M., Kuboi, R., Goto, Y., Clustering of fluorine-substituted alcohols as a factor responsible for their marked effects on proteins and peptides (1999) J Am Chem Soc, 121, pp. 8427-8433
  • Dalessio, P.M., Fromholt, S.E., Ropson, I.J., The role of Trp-82 in the folding of intestinal fatty acid binding protein (2005) Proteins, 61, pp. 176-183
  • Mukhopadhyay, K., Basak, S., Conformation induction in melanotropic peptides by trifluoroethanol: Fluorescence and circular dichroism study (1998) Biophys Chem, 74, pp. 175-186. , PMID: 9779581
  • Hackl, E.V., Limited proteolysis of natively unfolded protein 4E-BP1 in the presence of trifluoroethanol (2014) Biopolymers, 101, pp. 591-602. , PMID: 24122746
  • Benjwal, S., Verma, S., Röhm, K.-H., Gursky, O., Monitoring protein aggregation during thermal unfolding in circular dichroism experiments (2006) Protein Sci, 15, pp. 635-639. , PMID: 16452626
  • Curto, L.M., Angelani, C.R., Delfino, J.M., Intervening in the β-barrel structure of lipid binding proteins: Consequences on folding, ligand-binding and aggregation propensity (2015) Prostaglandins Leukot Essent Fat Acids., 93, pp. 37-43
  • Chiti, F., Dobson, C.M., Protein misfolding, functional amyloid, and human disease (2006) Annu Rev Biochem, 75, pp. 333-366. , PMID: 16756495
  • Romero, P., Obradovic, Z., Li, X., Garner, E.C., Brown, C.J., Dunker, A.K., Sequence complexity of disordered protein (2001) Proteins Struct Funct Genet, 42, pp. 38-48. , John Wiley & Sons, Inc.;
  • Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., Dunker, A.K., Exploiting heterogeneous sequence properties improves prediction of protein disorder (2005) Proteins Struct Funct Bioinforma, 61, pp. 176-182. , Wiley Subscription Services, Inc., A Wiley Company;
  • Peng, K., Vucetic, S., Radivojac, P., Brown, C.J., Dunker, A.K., Obradovic, Z., Optimizing long intrinsic disorder predictors with protein evolutionary information (2005) J Bioinform Comput Biol, 3, pp. 35-60. , Imperial College Press;
  • Xue, B., Dunbrack, R.L., Williams, R.W., Dunker, A.K., Uversky, V.N., PONDR-FIT: A meta-predictor of intrinsically disordered amino acids (2010) Biochim Biophys Acta-Proteins Proteomics, 1804, pp. 996-1010
  • Disfani, F.M., Hsu, W.-L., Mizianty, M.J., Oldfield, C.J., Xue, B., Dunker, A.K., MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins (2012) Bioinformatics, 28, pp. i75-83. , Oxford University Press;
  • Hoh, J.H., Functional protein domains from the thermally driven motion of polypeptide chains: A proposal (1998) Proteins Struct Funct Genet, 32, pp. 223-228. , Wiley Subscription Services, Inc., A Wiley Company;
  • Yeh, S.R., Ropson, I.J., Rousseau, D.L., Hierarchical folding of intestinal fatty acid binding protein (2001) Biochemistry, 40, pp. 4205-4210. , PMID: 11284675
  • Drozdetskiy, A., Cole, C., Procter, J., Barton, G.J., JPred4 : A protein secondary structure prediction server (2015) Nucleic Acids Res., 43, pp. 389-394
  • Lin, K., Simossis, V.A., Taylor, W.R., Heringa, J., A simple and fast secondary structure prediction method using hidden neural networks (2005) Bioinformatics, 21, pp. 152-159. , PMID: 15377504
  • Povey, J.F., Smales, C.M., Hassard, S.J., Howard, M.J., Comparison of the effects of 2, 2,2-trifluoroethanol on peptide and protein structure and function (2007) J Struct Biol, 157, pp. 329-338. , PMID 16979904
  • Sacchettini, J.C., Scapin, G., Gopaul, D., Gordon, J.I., Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-Angstrom resolution (1992) J Biol Chem, 267, pp. 23534-23545

Citas:

---------- APA ----------
Angelani, C.R., Caramelo, J.J., Curto, L.M. & Delfino, J.M. (2017) . Structural coalescence underlies the aggregation propensity of a β-barrel protein motif. PLoS ONE, 12(2).
http://dx.doi.org/10.1371/journal.pone.0170607
---------- CHICAGO ----------
Angelani, C.R., Caramelo, J.J., Curto, L.M., Delfino, J.M. "Structural coalescence underlies the aggregation propensity of a β-barrel protein motif" . PLoS ONE 12, no. 2 (2017).
http://dx.doi.org/10.1371/journal.pone.0170607
---------- MLA ----------
Angelani, C.R., Caramelo, J.J., Curto, L.M., Delfino, J.M. "Structural coalescence underlies the aggregation propensity of a β-barrel protein motif" . PLoS ONE, vol. 12, no. 2, 2017.
http://dx.doi.org/10.1371/journal.pone.0170607
---------- VANCOUVER ----------
Angelani, C.R., Caramelo, J.J., Curto, L.M., Delfino, J.M. Structural coalescence underlies the aggregation propensity of a β-barrel protein motif. PLoS ONE. 2017;12(2).
http://dx.doi.org/10.1371/journal.pone.0170607