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Structural biology

About: Structural biology is a research topic. Over the lifetime, 2206 publications have been published within this topic receiving 126070 citations.


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Journal ArticleDOI
TL;DR: A majority of targets have been expressed in advanced host systems and modified from their wild-type form with distinct focus on conformation and thermostabilisation, and strategies for native protein purification should also be considered where possible, particularly in light of the recent advances in single particle cryo electron microscopy.

47 citations

Book ChapterDOI
TL;DR: The methodology and recent application of expressed protein ligation and protein trans-splicing for NMR structural studies of proteins and protein complexes and the protocol used in the lab for the segmental isotopic labeling of a 50-kDa protein Csk (C-terminal Src kinase) using expressedprotein ligation methods are described.
Abstract: Nuclear magnetic resonance (NMR) spectroscopy has emerged as one of the principle techniques of structural biology. It is not only a powerful method for elucidating the three‐dimensional structures under near physiological conditions but also a convenient method for studying protein‐ligand interactions and protein dynamics. A major drawback of macromolecular NMR is its size limitation, caused by slower tumbling rates and greater complexity of the spectra as size increases. Segmental isotopic labeling allows for specific segment(s) within a protein to be selectively examined by NMR, thus significantly reducing the spectral complexity for large proteins and allowing for the application of a variety of solution‐based NMR strategies. Two related approaches are generally used in the segmental isotopic labeling of proteins: expressed protein ligation and protein trans ‐splicing. Here, we describe the methodology and recent application of expressed protein ligation and protein trans ‐splicing for NMR structural studies of proteins and protein complexes. We also describe the protocol used in our lab for the segmental isotopic labeling of a 50‐kDa protein Csk (C‐terminal Src kinase) using expressed protein ligation methods.

47 citations

Journal ArticleDOI
TL;DR: The current status in structural biology of the molecular complexes formed between heparin and its protein partners through the current concept of the heparIn interactome is discussed.

47 citations

Journal ArticleDOI
TL;DR: It is shown that quinary interactions can amplify and even reverse the mutational response of proteins, being a key aspect in pathogenic protein misfolding and aggregation.
Abstract: In cells, proteins are embedded in a crowded environment that controls their properties via manifold avenues including weak protein–macromolecule interactions. A molecular level understanding of these quinary interactions and their contribution to protein stability, function, and localization in the cell is central to modern structural biology. Using a mutational analysis to quantify the energetic contributions of single amino acids to the stability of the ALS related protein superoxide dismutase I (SOD1) in mammalian cells, we show that quinary interactions destabilize SOD1 by a similar energetic offset for most of the mutants, but there are notable exceptions: Mutants that alter its surface properties can even lead to a stabilization of the protein in the cell as compared to the test tube. In conclusion, quinary interactions can amplify and even reverse the mutational response of proteins, being a key aspect in pathogenic protein misfolding and aggregation.

47 citations

Journal ArticleDOI
TL;DR: The key to improved success with membrane protein structural elucidation is technology development, and the most efficient approach constitutes parallel studies on a large number of targets and evaluation of various systems for expression.
Abstract: Structural genomics, structure-based analysis of gene products, has so far mainly concentrated on soluble proteins because of their less demanding requirements for overexpression, purification and crystallisation compared to membrane proteins. This so-called "low-hanging fruit" approach has generated more than 25,000 structures deposited in databases. In contrast, the substantially more complex membrane proteins, in relation to all steps from overexpression to high-resolution structure determination, represent less than 1% of available crystal structures. This is in sharp contrast to the importance of this type of proteins, particularly G protein-coupled receptors (GPCRs), as today 60-70% of the current drug targets are based on membrane proteins. The key to improved success with membrane protein structural elucidation is technology development. The most efficient approach constitutes parallel studies on a large number of targets and evaluation of various systems for expression. Next, high throughput format solubilisation and refolding screening methods for a wide range of detergents and additives in numerous concentrations should be established. Today, several networks dealing with structural genomics approaches of membrane proteins have been initiated, among them the Membrane Protein Network (MePNet) programme that deals with the pharmaceutically important mammalian GPCRs. In MePNet, three overexpression systems have been employed for the evaluation of 101 GPCRs, which has generated large quantities of numerous recombinant GPCRs, compatible for structural biology applications.

47 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202335
202272
2021149
2020154
2019152
2018140