scholarly journals Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma

2021 ◽  
Vol 22 (4) ◽  
pp. 1766
Author(s):  
Yuki Kawata ◽  
Hisashi Hirano ◽  
Ren Takahashi ◽  
Yukari Miyano ◽  
Ayuko Kimura ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
In Silico ◽  
Disulfide Bonds ◽  
Protein Complexes ◽  
Bond Formation ◽  
Immunoglobulin A ◽  
Detailed Structure ◽  
J Chain ◽  
Noncovalent Bonds

Immunoglobulin A (IgA)-albumin complexes may be associated with pathophysiology of multiple myeloma, although the etiology is not clear. Detailed structural analyses of these protein–protein complexes may contribute to our understanding of the pathophysiology of this disease. We analyzed the structure of the IgA-albumin complex using various electrophoresis, mass spectrometry, and in silico techniques. The data based on the electrophoresis and mass spectrometry showed that IgA in the sera of patients was dimeric, linked via the J chain. Only dimeric IgA can bind to albumin molecules leading to IgA-albumin complexes, although both monomeric and dimeric forms of IgA were present in the sera. Molecular interaction analyses in silico implied that dimeric IgA and albumin interacted not only via disulfide bond formation, but also via noncovalent bonds. Disulfide bonds were predicted between Cys34 of albumin and Cys311 of IgA, resulting in an oxidized form of albumin. Furthermore, complex formation prolongs the half-life of IgA molecules in the IgA-albumin complex, leading to excessive glycation of IgA molecules and affects the accumulation of IgA in serum. These findings may demonstrate why complications such as hyperviscosity syndrome occur more often in patients with IgA dimer producing multiple myeloma.

Towards the Standard-Module Approach to Disulfide-Linked Polypeptide Nanostructures. I. Methodological Prerequisites and Mass Spectrometric Characterization of the Test Two-Loop Structure

2003 ◽  
Vol 9 (2) ◽  
pp. 139-148 ◽  
Author(s):  
O.A. Mirgorodskaya ◽  
K.F. Haselmann ◽  
F. Kjeldsen ◽  
R.A. Zubarev ◽  
P. Roepstorff
Keyword(s):  
Mass Spectrometry ◽  
Disulfide Bonds ◽  
Bond Cleavage ◽  
Bond Formation ◽  
Peptide Bond ◽  
Biologically Active ◽  
Loop Structure ◽  
Partial Acid Hydrolysis ◽  
Peptide Bond Cleavage

Potentially biologically-active nanostructures can be created from single chains of unmodified peptides by cross-linking different regions of the chain by disulfide bonds and cleaving the chain at specified sites to obtain the final configuration. The availability of techniques for assembly and characterization of such structures was tested on a two-loop structure created from a 21-residue linear peptide. Directed intra-molecular disulfide bond formation was performed by inserting partial sequences favoring intra-molecular S–S bond formation (“loops”) separated by partial sequences disfavoring such a process (“spacers”) into the precursor sequence. Peptide bond cleavage by partial acid hydrolysis at specific sites (GG, NP/DP) inside the loops opened them; the same process in the spacer separated the loops. Synthesis, oxidation and bond cleavage were monitored by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI ToF MS). The hydrolysis fragments of the produced nanostructures were characterized by tandem electrospray ionization Fourier transform mass spectrometry (ESI FT-MS) with collisional and electron capture dissociations. The latter technique was especially useful as it cleaves S–S bonds preferentially. The feasibility of the proposed synthesis approach and the adequacy of the analysis techniques for the test structure were demonstrated.

scholarly journals Ero1–PDI interactions, the response to redox flux and the implications for disulfide bond formation in the mammalian endoplasmic reticulum

2013 ◽  
Vol 368 (1617) ◽  
pp. 20110403 ◽  
Author(s):  
Adam M. Benham ◽  
Marcel van Lith ◽  
Roberto Sitia ◽  
Ineke Braakman
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Secretory Pathway ◽  
Protein Complexes ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Terminal Electron Acceptor ◽  
Post Translational Modifications

The protein folding machinery of the endoplasmic reticulum (ER) ensures that proteins entering the eukaryotic secretory pathway acquire appropriate post-translational modifications and reach a stably folded state. An important component of this protein folding process is the supply of disulfide bonds. These are introduced into client proteins by ER resident oxidoreductases, including ER oxidoreductin 1 (Ero1). Ero1 is usually considered to function in a linear pathway, by ‘donating’ a disulfide bond to protein disulfide isomerase (PDI) and receiving electrons that are passed on to the terminal electron acceptor molecular oxygen. PDI engages with a range of clients as the direct catalyst of disulfide bond formation, isomerization or reduction. In this paper, we will consider the interactions of Ero1 with PDI family proteins and chaperones, highlighting the effect that redox flux has on Ero1 partnerships. In addition, we will discuss whether higher order protein complexes play a role in Ero1 function.

Rapid Online Buffer Exchange: A Method for Screening of Proteins, Protein Complexes, and Cell Lysates by Native Mass Spectrometry

2019 ◽  
Author(s):  
Zachary VanAernum ◽  
Florian Busch ◽  
Benjamin J. Jones ◽  
Mengxuan Jia ◽  
Zibo Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Speed ◽  
Structural Information ◽  
Protein Complexes ◽  
High Sensitivity ◽  
Native Mass Spectrometry ◽  
Structural Features ◽  
Consumer Products ◽  
Cell Lysates ◽  
Protein Expression And Purification

It is important to assess the identity and purity of proteins and protein complexes during and after protein purification to ensure that samples are of sufficient quality for further biochemical and structural characterization, as well as for use in consumer products, chemical processes, and therapeutics. Native mass spectrometry (nMS) has become an important tool in protein analysis due to its ability to retain non-covalent interactions during measurements, making it possible to obtain protein structural information with high sensitivity and at high speed. Interferences from the presence of non-volatiles are typically alleviated by offline buffer exchange, which is timeconsuming and difficult to automate. We provide a protocol for rapid online buffer exchange (OBE) nMS to directly screen structural features of pre-purified proteins, protein complexes, or clarified cell lysates. Information obtained by OBE nMS can be used for fast (<5 min) quality control and can further guide protein expression and purification optimization.

Mass Spectrometry for Proteomics and Recent Developments in ESI, MALDI and other Ionization Methodologies

2019 ◽  
Vol 16 (4) ◽  
pp. 267-276
Author(s):  
Qurat ul Ain Farooq ◽  
Noor ul Haq ◽  
Abdul Aziz ◽  
Sara Aimen ◽  
Muhammad Inam ul Haq
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
New Technologies ◽  
Protein Complexes ◽  
Imaging Techniques ◽  
Desorption Electrospray Ionization ◽  
High Throughput Analysis ◽  
Enhanced Sensitivity ◽  
Recent Developments ◽  
The Way

Background: Mass spectrometry is a tool used in analytical chemistry to identify components in a chemical compound and it is of tremendous importance in the field of biology for high throughput analysis of biomolecules, among which protein is of great interest. Objective: Advancement in proteomics based on mass spectrometry has led the way to quantify multiple protein complexes, and proteins interactions with DNA/RNA or other chemical compounds which is a breakthrough in the field of bioinformatics. Methods: Many new technologies have been introduced in electrospray ionization (ESI) and Matrixassisted Laser Desorption/Ionization (MALDI) techniques which have enhanced sensitivity, resolution and many other key features for the characterization of proteins. Results: The advent of ambient mass spectrometry and its different versions like Desorption Electrospray Ionization (DESI), DART and ELDI has brought a huge revolution in proteomics research. Different imaging techniques are also introduced in MS to map proteins and other significant biomolecules. These drastic developments have paved the way to analyze large proteins of >200kDa easily. Conclusion: Here, we discuss the recent advancement in mass spectrometry, which is of great importance and it could lead us to further deep analysis of the molecules from different perspectives and further advancement in these techniques will enable us to find better ways for prediction of molecules and their behavioral properties.

Direct sequencing of a disulfide-linked peptide with electrospray ionization tandem mass spectrometry

The Analyst ◽  
2015 ◽  
Vol 140 (8) ◽  
pp. 2623-2627 ◽  
Author(s):  
Gongyu Li ◽  
Jiying Pei ◽  
Yue Yin ◽  
Guangming Huang
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Corona Discharge ◽  
Electrospray Ionization ◽  
Disulfide Bonds ◽  
Direct Sequencing ◽  
Peptide Sequencing ◽  
Tandem Mass ◽  
Esi Ms ◽  
Ionization Tandem Mass Spectrometry

Enhanced corona discharge was employed for in-spray dissociation of disulfide bonds, facilitating disulfide-containing peptide sequencing with ESI-MS/MS.

scholarly journals RNA-Centric Approaches to Profile the RNA–Protein Interaction Landscape on Selected RNAs

2021 ◽  
Vol 7 (1) ◽  
pp. 11 ◽  
Author(s):  
André P. Gerber
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Cell Protein ◽  
Transcriptional Regulatory Networks ◽  
Technological Advances

RNA–protein interactions frame post-transcriptional regulatory networks and modulate transcription and epigenetics. While the technological advances in RNA sequencing have significantly expanded the repertoire of RNAs, recently developed biochemical approaches combined with sensitive mass-spectrometry have revealed hundreds of previously unrecognized and potentially novel RNA-binding proteins. Nevertheless, a major challenge remains to understand how the thousands of RNA molecules and their interacting proteins assemble and control the fate of each individual RNA in a cell. Here, I review recent methodological advances to approach this problem through systematic identification of proteins that interact with particular RNAs in living cells. Thereby, a specific focus is given to in vivo approaches that involve crosslinking of RNA–protein interactions through ultraviolet irradiation or treatment of cells with chemicals, followed by capture of the RNA under study with antisense-oligonucleotides and identification of bound proteins with mass-spectrometry. Several recent studies defining interactomes of long non-coding RNAs, viral RNAs, as well as mRNAs are highlighted, and short reference is given to recent in-cell protein labeling techniques. These recent experimental improvements could open the door for broader applications and to study the remodeling of RNA–protein complexes upon different environmental cues and in disease.

Sign in / Sign up

Export Citation Format

Share Document