A new way to explore the world of extracellular protein interactions

Abstract

Eukaryotic genomes encode large numbers of proteins that are either secreted or have exposed extracellular domains. It is highly likely that these proteins facilitate many important biological processes: however, as yet, most remain uncharacterized. Progress in this area of research has been impaired by the lack of a robust screening system that can be used to investigate interactions between large numbers of different extracellular proteins. In this issue, Bushell et al. introduce AVEXIS (avidity-based extracellular interaction screen), a high-throughput screening procedure, which can be used to identify even weak extracellular protein interactions with extremely high confidence. This assay represents an important development in the field of network biology. By combining data from the AVEXIS system with data produced by classical or variant yeast two-hybrid methods, it will be possible to assemble binary protein interaction networks that connect extracellular and intracellular processes. This information will dramatically increase our ability to understand a wide range of physiological processes and facilitate the development of better therapeutic strategies.

The Extracellular Protein VlsE Is Destabilized Inside Cells

“…constitute approximately ~20%-30% of cellular proteins, so there could be more such destabilized proteins. 30 2) VlsE-FRET is stabilized by the carbohydrate crowder Ficoll yet destabilized in the cell. While PGK stability changes can be rationalized by simple volume exclusion both in a Ficoll matrix and in cells, explaining VlSE stability and folding will either require effects beyond crowding, or a structure-dependent volume exclusion mechanism.…”

Detailed Topology Mapping Reveals Substantial Exposure of the “Cytoplasmic” C-Terminal Tail (CTT) Sequences in HIV-1 Env Proteins at the Cell Surface

“…In contrast to truncated Env, the CTT-exposed Env contains an additional ∼130 amino acids that contain sequences that have been demonstrated to interact with cellular partners such as calmodulin [60], [61], TAK1, part of the canonical NF-κB pathway [62], and Lumen [63]. As we are just beginning to understand the extent of cell surface protein-protein interactions [64], [65], the presence of a large extracellular sequence as demonstrated for CTT-exposed Env may provide the physical substrate necessary for interactions with as yet undefined cellular partners that prevent segregation into viral budding sites.…”

Construction of a Large Extracellular Protein Interaction Network and Its Resolution by Spatiotemporal Expression Profiling

“…By integrating these extracellular networks with gene distribution data, maps of the intercellular recognition processes used by multicellular organisms to coordinate their cellular behaviors can be built. Critically, these extracellular interactions will provide the means to link up the currently more extensive intracellular protein interaction networks (55) and build models of how neighboring cells within a multicellular organism respond to external stimuli.…”