Renee D. JiJi

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Name: JiJi, Renee D.

Organization: University of Missouri , USA

Department: Department of Chemistry

Title: (PhD)

Chemicals
References

Role of Bilayer Characteristics on the Structural Fate of Aβ(1–40) and Aβ(25–40)

Co-reporter:Jian Xiong, Carol A. Roach, Olayinka O. Oshokoya, Robert P. Schroell, Rauta A. Yakubu, Michael K. Eagleburger, Jason W. Cooley, and Renee D. JiJi

Biochemistry 2014 Volume 53(Issue 18) pp:

Publication Date(Web):April 4, 2014

DOI:10.1021/bi4016296

The β-amyloid (Aβ) peptide is derived from the transmembrane (TM) helix of the amyloid precursor protein (APP) and has been shown to interact with membrane surfaces. To understand better the role of peptide–membrane interactions in cell death and ultimately in Alzheimer’s disease, a better understanding of how membrane characteristics affect the binding, solvation, and secondary structure of Aβ is needed. Employing a combination of circular dichroism and deep-UV resonance Raman spectroscopies, Aβ(25–40) was found to fold spontaneously upon association with anionic lipid bilayers. The hydrophobic portion of the disease-related Aβ(1–40) peptide, Aβ(25–40), has often been used as a model for how its legacy TM region may behave structurally in aqueous solvents and during membrane encounters. The structure of the membrane-associated Aβ(25–40) peptide was found to depend on both the hydrophobic thickness of the bilayer and the duration of incubation. Similarly, the disease-related Aβ(1–40) peptide also spontaneously associates with anionic liposomes, where it initially adopts mixtures of disordered and helical structures. The partially disordered helical structures then convert to β-sheet structures over longer time frames. β-Sheet structure is formed prior to helical unwinding, implying a model in which β-sheet structure, formed initially from disordered regions, prompts the unwinding and destabilization of membrane-stabilized helical structure. A model is proposed to describe the mechanism of escape of Aβ(1–40) from the membrane surfaces following its formation by cleavage of APP within the membrane.

Quantification of protein secondary structure content by multivariate analysis of deep-ultraviolet resonance Raman and circular dichroism spectroscopies

Co-reporter:Olayinka O. Oshokoya, Carol A. Roach and Renee D. JiJi

Analytical Methods 2014 vol. 6(Issue 6) pp:1691-1699

Publication Date(Web):24 Jan 2014

DOI:10.1039/C3AY42032A

Determination of protein secondary structure (α-helical, β-sheet, and disordered motifs) has become an area of great importance in biochemistry and biophysics as protein secondary structure is directly related to protein function and protein related diseases. While NMR and X-ray crystallography can predict the placement of each atom in a protein to within an angstrom, optical methods (i.e. CD, Raman, and IR) are the preferred techniques for rapid evaluation of protein secondary structure content. Such techniques require calibration data to predict unknown protein secondary structure content where accuracy may be improved with the application of multivariate analysis. Here, a comparison of the protein secondary structure predictions obtained from multivariate analysis of ultraviolet resonance Raman (UVRR) and circular dichroism (CD) spectroscopic data using classical least squares (CLS), partial least squares (PLS), and multivariate curve resolution-alternating least squares (MCR-ALS) is made. Results of the multivariate analysis suggest that CD measurements provide more accurate prediction of protein α-helical content whereas UVRR more accurately predicts β-sheet content, an observation that is consistent with previous studies. Based on this analysis, it is suggested that the best approach to rapid and accurate protein secondary structure determination is to combine both CD and UVRR spectroscopic data.

Effects of fluidity on the ensemble structure of a membrane embedded -helical peptide

Co-reporter:Michael K. Eagleburger;Jason W. Cooley

Biopolymers 2014 Volume 101( Issue 8) pp:895-902

Publication Date(Web):

DOI:10.1002/bip.22472

ABSTRACT

Melittin, the main hemolytic component of honeybee venom, is unfolded in an aqueous environment and folds into an α-helical conformation in a lipid environment. Membrane fluidity is known to affect the activity and structure of melittin. By combining two structurally sensitive optical methods, circular dichroism (CD) and deep-ultraviolet resonance Raman spectroscopy (dUVRR), we have identified distinct structural fluctuations in melittin correlated with increased and decreased 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer fluidities. CD spectra have reduced intensity at temperatures above 22°C and high concentrations of the cholesterol analog 5α-cholestan-3β-ol indicating distortions in the α-helical structure under these conditions. No increase in the amide S is observed in the temperature-dependent dUVRR spectra, suggesting an increase in 3₁₀-helical structure with increasing temperatures above 22°C. However, incorporation of 25 mol% 5α-cholestan-3β-ol resulted in a small increase in the amide S intensity indicating partial unfolding of melittin. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 895–902, 2014.

Evolution of quantitative methods in protein secondary structure determination via deep-ultraviolet resonance Raman spectroscopy

Co-reporter:Carol A. Roach, John V. Simpson and Renee D. JiJi

Analyst 2012 vol. 137(Issue 3) pp:555-562

Publication Date(Web):06 Dec 2011

DOI:10.1039/C1AN15755H

Deep-ultraviolet resonance Raman (DUVRR) spectra is sensitive to secondary structural motifs but, similar to circular dichroism (CD) and infrared spectroscopy, requires the application of multivariate and advanced statistical analysis methods to resolve the pure secondary structure Raman spectra (PSSRS) for determination of secondary structure composition. Secondary structure motifs are selectively enhanced by different excitation wavelengths, a characteristic that inspired the first methods for quantifying secondary structures by DUVRR. This review traces the evolution of multivariate methods and their application to secondary structure composition analyses of proteins by DUVRR spectroscopy from the first experiments using two-wavelengths, and culminating with recent studies utilizing time-resolved DUVRR measurements.

Pre-processing of ultraviolet resonance Raman spectra

Co-reporter:John V. Simpson, Olayinka Oshokoya, Nicole Wagner, Jing Liu and Renee D. JiJi

Analyst 2011 vol. 136(Issue 6) pp:1239-1247

Publication Date(Web):26 Jan 2011

DOI:10.1039/C0AN00774A

The application of UV excitation sources coupled with resonance Raman have the potential to offer information unavailable with the current inventory of commonly used structural techniques including X-ray, NMR and IR analysis. However, for ultraviolet resonance Raman (UVRR) spectroscopy to become a mainstream method for the determination of protein secondary structure content and monitoring protein dynamics, the application of multivariate data analysis methodologies must be made routine. Typically, the application of higher order data analysis methods requires robust pre-processing methods in order to standardize the data arrays. The application of such methods can be problematic in UVRR datasets due to spectral shifts arising from day-to-day fluctuations in the instrument response. Additionally, the non-linear increases in spectral resolution in wavenumbers (increasing spectral data points for the same spectral region) that results from increasing excitation wavelengths can make the alignment of multi-excitation datasets problematic. Last, a uniform and standardized methodology for the subtraction of the water band has also been a systematic issue for multivariate data analysis as the water band overlaps the amide I mode. Here we present a two-pronged preprocessing approach using correlation optimized warping (COW) to alleviate spectra-to-spectra and day-to-day alignment errors coupled with a method whereby the relative intensity of the water band is determined through a least-squares determination of the signal intensity between 1750 and 1900 cm−1 to make complex multi-excitation datasets more homogeneous and usable with multivariate analysis methods.

Resolution of localized small molecule–Aβ interactions by deep-ultraviolet resonance Raman spectroscopy

Co-reporter:Mingjuan Wang, Renee D. JiJi

Biophysical Chemistry 2011 Volume 158(2–3) pp:96-103

Publication Date(Web):October 2011

DOI:10.1016/j.bpc.2011.05.017

The mechanism by which flavonoids prevent formation of amyloid-β (Aβ) fibrils, as well as how they associate with non-fibrillar Aβ is still unclear. Fresh, un-oxidized myricetin exhibited excitation and emission fluorescence maxima at 481 and 531 nm, respectively. Introduction of either Aβ(1–42) or Aβ(25–40) resulted in a fluorescence decrease, when measured at 481 nm, suggesting formation of a myricetin–Aβ complex. Circular dichroism (CD) and ultraviolet resonance Raman (UVRR) studies indicate that the association of myricetin with the Aβ peptide or its hydrophobic fragment, Aβ(25–40), leads to subtle changes in each peptide's conformation. Aβ(25–40) formed amyloid fibrils at a similar rate, when compared to the full-length peptide, Aβ(1–42), using thioflavin T (ThT) fluorescence. Studies also indicated that myricetin was equally effective at preventing the formation of both Aβ(1–42) and Aβ(25–40) fibrils. Although ThT assays indicated that Aβ(1–16) did not form amyloid fibrils, CD studies of the hydrophilic fragment, Aβ(1–16), suggest possible interactions between myricetin and aromatic side chains. UVRR studies of the full-length peptide and Aβ(1–16) showed increases in the intensity of the aromatic modes upon introduction of myricetin. Our findings suggest that myricetin interacts with soluble Aβ via two mechanisms, association with the hydrophobic C-terminal region and interactions with the aromatic side chains.Highlights► The short hydrophobic peptide, Aβ(25–40), exhibits a similar aggregation propensity to the full-length Aβ peptide. ► The flavonoid myricetin inhibits Aβ(1–42) and Aβ(25–40) fibril formation. ► Deep-UVRR studies indicate that myricetin may interact with aromatic residues of Aβ. ► CD, UVRR and fluorescence studies indicate non-aromatic myricetin–Aβ interactions at the hydrophobic C-terminus.

Application of EEM fluorescence in combination with PARAFAC analysis to simultaneously monitor quercetin in its deprotonated, aggregated, and protein bound states

Co-reporter:John V. Simpson;Marissa Burke

Journal of Chemometrics 2011 Volume 25( Issue 3) pp:101-108

Publication Date(Web):

DOI:10.1002/cem.1325

Abstract

Flavonoids, a group of naturally occurring polyphenols, attract great interest due to their many apparent health benefits including their anti-oxidant properties and anti-amyloidogenic properties. However, the behavior of flavonoids in aqueous environments can be unpredictable due to the potential formation of aggregates and hydrolysis products. A better understanding of the complex behavior of flavonoids is needed before flavonoid-based therapies can be developed. Employing excitation–emission matrix (EEM) fluorescence in combination with weighted-parallel factor analysis (WPARAFAC), a series of aqueous quercetin solutions were characterized at varying pH values and concentrations. Distinct pH and concentration-dependent fluorophores were observed with emission maxima of 540 and 600 nm, respectively. However, the excitation maxima of the two species were broad and highly overlapped ranging from 350 to 400 nm. In addition, the fluorescence of quercetin was characterized in the presence and absence of bovine serum albumin (BSA). Interaction with BSA resulted in a dramatic red-shift of the excitation maximum to 445 nm, while the emission maximum of the BSA–quercetin complex was slightly blue-shifted to 535 nm. Coupling of WPARAFAC and EEM fluorescence enabled simultaneous detection of multiple fluorescent quercetin species in solution at a wide range of conditions. Copyright © 2010 John Wiley & Sons, Ltd.

MCR-ALS analysis of two-way UV resonance Raman spectra to resolve discrete protein secondary structural motifs

Co-reporter:John V. Simpson, Gurusamy Balakrishnan and Renee D. JiJi

Analyst 2009 vol. 134(Issue 1) pp:138-147

Publication Date(Web):25 Nov 2008

DOI:10.1039/B814392G

The ability of ultraviolet resonance Raman (UVRR) spectroscopy to monitor a host of structurally sensitive protein vibrational modes, the amide I, II, III and S regions, makes it a potentially powerful tool for the visualization of equilibrium and non-equilibrium secondary structure changes in even the most difficult peptide samples. However, it is difficult to unambiguously resolve discrete secondary structure-derived UVRR spectral signatures independently of one another as each contributes an unknown profile to each of the spectrally congested vibrational modes. This limitation is compounded by the presence of aromatic side chains, which introduce additional overlapping vibrational modes. To address this, we have exploited an often overlooked tool for alleviating this spectral overlap by utilizing the differential excitability of the vibrational modes associated with α-helices and coil moieties, in the deep UV. The differences in the resonance enhancements of the various structurally associated vibrational modes yields an added dimensionality in the spectral data sets making them multi-way in nature. Through a ‘chemically relevant’ shape-constrained multivariate curve resolution-alternating least squares (MCR-ALS) analysis, we were able to deconvolute the complex amide regions in the multi-excitation UVRR spectrum of the protein myoglobin, giving us potentially useful ‘pure’ secondary structure-derived contributions to these individual vibrational profiles.

Insights into the aggregation mechanism of Aβ(25–40)

Co-reporter:Jian Xiong, Renee D. JiJi

Biophysical Chemistry (January 2017) Volume 220() pp:

Publication Date(Web):January 2017

DOI:10.1016/j.bpc.2016.11.003

•Substitution of alanine at position 32 or 37 shifts the oligomeric distribution from tetramers/trimers to trimers/dimers.•Increased backbone hydration reduces Aβ(25–40)'s propensity to fibrillize.•Structural changes in Aβ(25–40) induced by myricetin are eliminated when the hydrophobicity at residue 32 is reduced.•Fibrillization depletes the store of the largest oligomeric species, with little impact on the amountof smaller oligomers.The hydrophobic fragment of the Alzheimer's related β-amyloid (Aβ) peptide, Aβ(25–40), aggregates and forms insoluble amyloid fibrils at a rate similar to the full-length peptide. In order to gain insight into the fibrillization of Aβ(25–40) and the ability of the flavonoid myricetin to inhibit its aggregation, the isoleucine at position 32 (I32A) and the glycine at position 37 (G37A) in the full-length peptide were replaced with alanine. Thioflavin T assays indicate that substitution of isoleucine for alanine significantly reduces the rate and extent of fibrillization compared to the Aβ(25–40) and G37A peptides. Although all three peptides are fully disordered initially, circular dichroism studies suggest the structure of the I32A and G37A peptides are different from the parent peptide Aβ(25–40). Introduction of myricetin to the peptide samples results in modest structural changes for the Aβ(25–40) and G37A peptides but not the I32A peptide. Aβ(25–40) oligomers were predominantly tetramers, whereas I32A and G37A oligomers were a mixture of trimers and dimers. After 48 h of incubation at 37 °C, the amount of tetramers and trimers in solution dropped for the Aβ(25–40) and G37A peptides but remained similar for the I32A peptide. Incubation of Aβ(25–40) with myricetin increased the relative proportion of trimers to tetramers. Ultraviolet resonance Raman studies suggests that the I32A peptide may be more hydrated than the Aβ(25–40) and G37A peptides. Taken together, these data indicate the structural changes observed for the Aβ(25–40) and G37A peptides upon introduction of myricetin are localized around residue 32 and could arise from hydrophobic interactions between the peptide and the flavonoid or interference with the self-association of the peptide in this region. Substitution of isoleucine at position 32 with alanine had little effect on the peptide's secondary structure but dramatically decreased the propensity of the peptide fibrillize.

Quantification of protein secondary structure content by multivariate analysis of deep-ultraviolet resonance Raman and circular dichroism spectroscopies

Co-reporter:Olayinka O. Oshokoya;Carol A. Roach

Analytical Methods (2009-Present) 2014 - vol. 6(Issue 6) pp:NaN1699-1699

Publication Date(Web):2014/02/27

DOI:10.1039/C3AY42032A