抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Traveling wave ion mobility spectrometry (TW IMS) is a new IMS method implemented in the Synapt IMS/mass spectrometry system (Waters). Despite its wide adoption, the foundations of TW IMS were only qualitatively understood and factors governing the ion transit time (the separation parameter) and resolution remained murky. Here we develop the theory of TW IMS using derivations and ion dynamics simulations. The key parameter is the ratio (c) of ion drift velocity at the steepest wave slope to wave speed. At low c, the ion transit velocity is proportional to the squares of mobility (K) and electric field intensity (E), as opposed to linear scaling in drift tube (DT) IMS and differential mobility analyzers. At higher c, the scaling deviates from quadratic in a way controlled by the waveform profile, becoming more gradual with the ideal triangular profile but first steeper and then more gradual for realistic profiles with variable E. At highest c, the transit velocity asymptotically approaches the wave speed. ...

Fundamentals of Traveling Wave Ion Mobility Spectrometry

Although nonnative protein conformations, including intermediates along the folding pathway and kinetically trapped misfolded species that disfavor the native state, are rarely isolated in the solution phase, they are often stable in the gas phase, where macromolecular ions from electrospray ionization can exist in varying charge states. Differences in the structures of nonnative conformations in the gas phase are often large enough to allow different shapes and charge states to be separated because of differences in their mobilities through a gas. Moreover, gentle collisional activation can be used to induce structural transformations. These new structures often have different mobilities. Thus, there is the possibility of developing a multidimensional separation that takes advantage of structural differences of multiple stable states. This review discusses how nonnative states differ in the gas phase compared with solution and presents an overview of early attempts to utilize and manipulate structures in...

Biomolecule Analysis by Ion Mobility Spectrometry

The use of ion mobility separation to determine the collision cross-section of a gas-phase ion can provide valuable structural information. The introduction of travelling-wave ion mobility within a quadrupole/time-of-flight mass spectrometer has afforded routine collision cross-section measurements to be performed on a range of ionic species differing in gas-phase size/structure and molecular weight at physiologically relevant concentrations. Herein we discuss the technical advances in the second-generation travelling-wave ion mobility separator, which result in up to a four-fold increase in mobility resolution. This improvement is demonstrated using two reverse peptides (mw 490 Da), small ruthenium-containing anticancer drugs (mw 427 Da), a cisplatin-modified protein (mw 8776 Da) and the noncovalent tetradecameric chaperone complex GroEL (mw 802 kDa). What is also shown are that the collision cross-sections determined using the second-generation mobility separator correlate well with the previous generation and theoretically derived values.

Enhancements in travelling wave ion mobility resolution

Ion Mobility Spectrometry (IMS) is a widely used and ‘well-known’ technique of ion separation in the gaseous phase based on the differences in ion mobilities under an electric field All IMS instruments operate with an electric field that provides space separation, but some IMS instruments also operate with a drift gas flow that provides also a temporal separation In this review we will summarize the current IMS instrumentation IMS techniques have received an increased interest as new instrumentation and have become available to be coupled with mass spectrometry (MS) For each of the eight types of IMS instruments reviewed it is mentioned whether they can be hyphenated with MS and whether they are commercially available Finally, out of the described devices, the six most-consolidated ones are compared The current review article is followed by a companion review article which details the IMS hyphenated techniques (mainly gas chromatography and mass spectrometry) and the factors that make the data from an IMS device change as a function of device parameters and sampling conditions These reviews will provide the reader with an insightful view of the main characteristics and aspects of the IMS technique

Review on Ion Mobility Spectrometry. Part 1: Current Instrumentation

https://link.springer.com/content/pdf/10.1016%2Fj.jasms.2008.11.022.pdf

Overtone mobility spectrometry: part 1. Experimental observations.

Multidimensional separations combined with mass spectrometry are used to study the proteins that are present in two states of Drosophila melanogaster: the whole embryo and the adult head. The approach includes the incorporation of a gas-phase separation dimension in which ions are dispersed according to differences in their mobilities and is described as a means of providing a detailed analytical map of the proteins that are present. Overall, we find evidence for 1133 unique proteins. In total, 780 are identified in the head, and 660 are identified in the embryo. Only 307 proteins are in common to both developmental stages, indicating that there are significant differences in these proteomes. A comparison of the proteome to a database of mRNAs that are found from analysis by cDNA approaches (i.e., transcriptome) also shows little overlap. All of this information is discussed in terms of the relationship between the predicted genome, and measured transcriptomes and proteomes. Additionally, the merits and weaknesses of current technologies are assessed in some detail.

Mapping the proteome of Drosophila melanogaster: analysis of embryos and adult heads by LC-IMS-MS methods.

Ion mobility spectrometry techniques (IMS and IMS-IMS) combined with collision-induced dissociation (CID) and mass spectrometry (MS) are used to investigate the structures of singly-lithiated carbohydrate isomers. With the exception of some favorable cases, IMS-MS analyses of underivatized carbohydrates reveal that most isobaric precursor ions have similar collision cross sections (ccs). In contrast, ccs values for isomeric fragment ions obtained by IMS-CID-IMS-MS analysis are often different, and thus appear to be useful as a means of distinguishing the isomeric precursors. We report values of ccs (in He) for precursor- and associated-fragment ions for three monosaccharide isomers (glucose, galactose and fructose), ten disaccharide isomers (sucrose, leucrose, palatinose, trehalose, cellobiose, β-gentiobiose, isomaltose, maltose, lactose and melibiose), and three trisaccharide isomers (raffinose, melezitose and maltotriose). These values are discussed as a means of differentiating precursor carbohydrates.

Investigating carbohydrate isomers by IMS-CID-IMS-MS: precursor and fragment ion cross-sections

When a packet of ions in a buffer gas is exposed to a weak electric field, the ions will separate according to differences in their mobilities through the gas. This separation forms the basis of the analytical method known as ion mobility spectroscopy and is highly efficient, in that it can be carried out in a very short time frame (micro- to milliseconds). Recently, efforts have been made to couple the approach with liquid-phase separations and mass spectrometry in order to create a high-throughput and high-coverage approach for analyzing complex mixtures. This article reviews recent work to develop this approach for proteomics analyses. The instrumentation is described briefly. Several multidimensional data sets obtained upon analyzing complex mixtures are shown in order to illustrate the approach as well as provide a view of the limitations and required future work.

Developing liquid chromatography ion mobility mass spectometry techniques.

Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of ion mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with principal component analysis (PCA) for characterizing serum N-linked glycans from 81 individuals: 28 with cirrhosis of the liver, 25 with liver cancer, and 28 apparently healthy. Supervised PCA of combined ion-mobility profiles for several, to as many as 10 different mass-to-charge ratios for glycan ions, improves the delineation of diseased states. This extends an earlier study [J. Proteome Res.2008, 7, 1109–1117] of isomers associated with a single glycan (S1H5N4) in which PCA analysis of the IMS profiles appeared to differentiate the liver cancer group from the other samples. Although performed on a limited number of test subjects, ...

Ruwan T. Kurulugama

Papers

Overtone mobility spectrometry: part 1. Experimental observations.

Mapping the proteome of Drosophila melanogaster: analysis of embryos and adult heads by LC-IMS-MS methods.

Investigating carbohydrate isomers by IMS-CID-IMS-MS: precursor and fragment ion cross-sections

Developing liquid chromatography ion mobility mass spectometry techniques.

Delineating diseases by IMS-MS profiling of serum N-linked glycans.