Investigation of stable and transient protein–protein interactions: Past, present, and future

Wetie, Armand G. Ngounou; Sokolowska, Izabela; Woods, Alisa G.; Roy, Urmi; Loo, Joseph A.; Darie, Costel C.

doi:10.1002/pmic.201200328

Cited by 130 publications

(111 citation statements)

References 198 publications

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“…We expect that recent strategies to analyze protein complexes using quantitative MS will further improve our understanding of such molecular clusters. [187][188][189][190][191] In addition, quantitative MS-based profiling methods for cell organelles can provide information about the spatial distribution of proteins 192,193 and reveal dynamic changes in this distribution. Given the role of circulating platelets as sentinels of vascular integrity, proteomic analyses and PTM signatures could lead to new approaches for diagnosis and treatment of platelet disorders.…”

Section: Future Directions Of Platelet Proteomicsmentioning

confidence: 99%

What Can Proteomics Tell Us About Platelets?

Burkhart

Gambaryan

Watson

et al. 2014

Circulation Research

105

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More than 130 years ago, it was recognized that platelets are key mediators of hemostasis. Nowadays, it is established that platelets participate in additional physiological processes and contribute to the genesis and progression of cardiovascular diseases. Recent data indicate that the platelet proteome, defined as the complete set of expressed proteins, comprises >5000 proteins and is highly similar between different healthy individuals. Owing to their anucleate nature, platelets have limited protein synthesis. By implication, in patients experiencing platelet disorders, platelet (dys)function is almost completely attributable to alterations in protein expression and dynamic differences in post-translational modifications. Modern platelet proteomics approaches can reveal (1) quantitative changes in the abundance of thousands of proteins, (2) post-translational modifications, (3) protein–protein interactions, and (4) protein localization, while requiring only small blood donations in the range of a few milliliters. Consequently, platelet proteomics will represent an invaluable tool for characterizing the fundamental processes that affect platelet homeostasis and thus determine the roles of platelets in health and disease. In this article we provide a critical overview on the achievements, the current possibilities, and the future perspectives of platelet proteomics to study patients experiencing cardiovascular, inflammatory, and bleeding disorders.

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Section: Future Directions Of Platelet Proteomicsmentioning

confidence: 99%

What Can Proteomics Tell Us About Platelets?

Burkhart

Gambaryan

Watson

et al. 2014

Circulation Research

105

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“…While DESI has also been adapted to study large biomolecules, via the mixing of ES droplets and solution in a process known as liquid DESI,5, 6 it has not yet been applied to proteins deposited on surfaces and desorbed in solutions that retain their native state interactions. Despite considerable progress in applications of non‐denaturing or native MS (nMS) of soluble7, 8, 9 and membrane embedded proteins10 the possibility of effectively “lifting” intact complexes from surfaces is desirable since many high throughput technologies then become accessible 11. Moreover the lipid distribution in natural membranes is essentially planar and asymmetric with varying spatial and temporal arrangements in the vicinity of embedded protein complexes 12.…”

mentioning

confidence: 99%

Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces

et al. 2017

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Mass spectrometry (MS) applications for intact protein complexes typically require electrospray (ES) ionization and have not been achieved via direct desorption from surfaces. Desorption ES ionization (DESI) MS has however transformed the study of tissue surfaces through release and characterisation of small molecules. Motivated by the desire to screen for ligand binding to intact protein complexes we report the development of a native DESI platform. By establishing conditions that preserve non‐covalent interactions we exploit the surface to capture a rapid turnover enzyme–substrate complex and to optimise detergents for membrane protein study. We demonstrate binding of lipids and drugs to membrane proteins deposited on surfaces and selectivity from a mix of related agonists for specific binding to a GPCR. Overall therefore we introduce this native DESI platform with the potential for high‐throughput ligand screening of some of the most challenging drug targets including GPCRs.

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“…Even a brief exposure to denaturing conditions is expected to result in protein unfolding and dissociation of non-covalent interactions for at least some complexes. However, certain non-covalent interactions, including coordination of metal ions and multisubunit protein-protein interactions, can be stable at such conditions [353][354][355]. We anticipated that the reconstituted RP extracts would contain non-covalent complexes that were (a) stable enough to survive the denaturing conditions and (b) re-assembled after the buffer exchange to native conditions.…”

Section: -3)mentioning

confidence: 99%

Top-down proteomic analysis of protein pharmaceuticals, mixtures of protein complexes, and ribosomal protein extracts by capillary zone electrophoresis-mass spectrometry

Belov¹

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Investigation of stable and transient protein–protein interactions: Past, present, and future

Cited by 130 publications

References 198 publications

What Can Proteomics Tell Us About Platelets?

What Can Proteomics Tell Us About Platelets?

Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces

Top-down proteomic analysis of protein pharmaceuticals, mixtures of protein complexes, and ribosomal protein extracts by capillary zone electrophoresis-mass spectrometry

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