Special Issue: Protein Structure and Proteomics





The 18th International Methods in Protein Structure Analysis (MPSA) conference was held in Uppsala, Sweden in August 2010. These meetings bring together scientists in various fields to discuss new methods for protein analysis. The reviews in this Special Issue highlight some of the exciting research presented at the meeting, including a focus on protein misfolding in disease

The 18th International Conference of Methods in Protein Structure Analysis (MPSA) was held in Uppsala, Sweden in August 2010. MPSA meetings bring together researchers in protein chemistry, including proteomics and structural biology, and highlight the use of these techniques to address biological questions. The collection of minireviews in this Special Issue of FEBS Journal stemming from the conference highlight: (a) methods for proteomic analysis and bioinformatics; (b) protein folding and interactions with membranes; and (c) proteins in the immune response.

The analysis of proteomes is critical for understanding biological processes. Zhou et al. describe the use of proteome reactors for sample processing; Ino and Hirano report a method for direct analysis of peptides from membranes by MALDI-TOF MS. Landreh et al. describe a method for monitoring of protein folding by hydrogen/deuterium exchange. Finally, Van Damme et al. detail ways in which to monitor protein α-N acetyllation and its biological consequences. Analysis of the vast amount of collected data is a challenge for proteomic and protein chemistry studies. The MACiE database, described by Holliday et al., is a useful tool for analyzing the complexity of enzyme folds and mechanisms, allowing users to explore amino acid and cofactor representation in enzymatic reactions.

Protein (mis)folding, and interaction with membranes were conference themes in 2010. Martínez-Gil et al. summarize the mechanisms by which proteins are targeted to and inserted into the endoplasmic reticulum membrane. Roussel et al. detail the pathobiology of serpinopathies, a group of diseases typified by mutations of α1-antitrypsin and neuroserpin that result in defects in protein folding.

Protein misfolding leading to amyloid formation is a hallmark of several diseases, including Alzheimer’s disease and type II diabetes. Therefore, understanding the determinants of amyloid formation and its effects is critical for future therapeutic interventions. Five minireviews in this issue focus on such aspects. Eichner and Radford outline advances in the folding and aggregation mechanisms of the amyloidogenic protein β2-microglobulin. Recent studies on the use of disulfide engineering to stabilize Aβ-aggregates for structural studies are detailed by Härd. Willander et al. report on the role of BRICHOS domain-containing proteins in preventing the misfolding of proteins with high β-sheet propensity. In addition to protein aggregation, the interaction of amyloid proteins with membranes is also an aspect of their cytotoxicity. Williams and Serpell highlight recent studies on the binding of amyloid proteins to different types of biomimetic membrane models. Finally, Westermark and Westermark detail the pathogenesis of two amyloidoses.

The innate immune response relies on specific antimicrobial proteins as part of the initial defense. Veldhuizen et al. describe the structures of C-type lectin domains of collectins, which can bind glycoconjugates on foreign proteins. Cederlund et al. describe the structures, mechanism of action and regulation of two classes of endogenous antimicrobial peptide.

The minireviews included in this Special Issue are a sample of the protein chemistry research presented at the biennial MPSA meetings. We believe that the wide range of topics and diverse interests of the attendees engender creative thinking and foster novel approaches to unanswered questions.

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[ Ettore Appella is Chief of the Chemical Immunology Section, Laboratory of Cell Biology, National Cancer Institute, NIH. He received his MD from University of Rome, Italy, and then undertook postdoctoral studies at Johns Hopkins University. His research interests encompass protein chemistry, immunology, and the synthesis of small organic molecules that target HIV, p53, and Wip1. ]

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[ Jan Johansson received an MD and PhD from Karolinska Institutet in Stockholm in 1991. He was then a postdoctoral student at the ETH Zurich during 1992–1993. Since 2002, he has been a professor of medical biochemistry at the Swedish University of Agricultural Sciences in Uppsala, and since 2011 he has also been professor of biological dementia research at Karolinska Institutet. His current research includes the development of synthetic proteins for the treatment of lung disease, and studies of natural ways to control protein assembly phenomena in the prevention of amyloid formation and the regulation of spider silk formation. ]