Monitoring and modeling of protein processes using mass spectrometry, circular dichroism, and multivariate curve resolution methods
Monitoring and modeling of protein processes using mass spectrometry, circular dichroism, and multivariate curve resolution methods
Engineering Village 2
? 2006 Elsevier Inc
Accession number: 063010030787
Title: Monitoring and modeling of protein processes using mass spectrometry, circular dichroism, and multivariate curve resolution methods
Authors: Navea, Susana; Tauler, Roma; De Juan, Anna
Author affiliation: Chemometrics Group, Department of Analytical Chemistry, Universitat de Barcelona, 08028 Barcelona, Spain
Serial title: Analytical Chemistry
Abbreviated serial title: Anal. Chem.
Volume: v 78
Issue: n 14
Issue date: Jul 15 2006
Publication year: 2006
Pages: p 4768-4778
Language: English
ISSN: 0003-2700
CODEN: ANCHAM
Document type: Journal article (JA)
Publisher: American Chemical Society, Columbus, OH 43210-3337, United States
Abstract: Mass spectrometry has recently become one of the major analytical tools to study biomolecular structure and function. Ionization techniques, such as electrospray ionization (ESI), desorb biomolecules from solution to the gas phase keeping practically intact their natural structure. ESI applied to a protein solution produces a mixture of multiply charged ions, the ion charge distribution of which depends on the oligomeric form (mass) and on the protein surface exposed (amount of accommodated charges) of the related protein conformation. ESI-MS provides an efficient way to monitor protein processes; however, the ionic contributions of the different protein conformations involved usually overlap, and the use of chemometric tools is necessary to unravel the information related to the pure conformations that the biomolecule adopts along the process. Multivariate curve resolution-alternating least squares applied to MS-monitored protein processes provides the concentration profiles associated with the different protein conformations occurring during the process and the related pure mass spectra. The concentration profiles, in this context, the ionic contributions, describe the process mechanism and the structural information derived from the pure mass spectra characterizes the involved conformations. Mass spectra can be expressed schematically through percentages of base peak intensity. This chemical transformation compresses significantly the raw spectra and allows for an easier application of natural MS-related constraints, such as the presence of only one maximum, i.e., the base peak of a particular conformation, into the resolution of the pure signals. The combination of mass spectrometry and multivariate curve resolution methods is used to elucidate the mechanism of the pH-induced conformation changes of the bovine ?-lactoglobulin. As a final step, MS data are fused with circular dichroism data and are simultaneously analyzed to ensure and confirm that all the previously detected MS conformations really exist in solution and are an artifact of neither the ionization process nor their chemometric resolution. ? 2006 American Chemical Society.
Number of references: 31
Ei main heading: Proteins
Ei controlled terms: Ionization - Conformations - Mass spectrometers - pH - Molecular structure - Oligomers
Uncontrolled terms: Electrospray ionization (ESI) - Biomolecules - Protein processes - Gas phase
Ei classification codes: 804.1 Organic Compounds - 802.2 Chemical Reactions - 801.4 Physical Chemistry - 943.3 Special Purpose Instruments - 801.1 Chemistry, General - 815.1.1 Organic Polymers
Treatment: Theoretical (THR); Experimental (EXP)
DOI: 10.1021/ac052257r
Database: Compendex
Compilation and indexing terms, ? 2006 Elsevier Inc. All rights reserved
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