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Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity.

ABSTRACT: Nck is a functionally versatile multidomain adaptor protein consisting of one SH2 and three SH3 domains. In most cases, the SH2 domain mediates binding to tyrosine-phosphorylated receptors or cytosolic proteins, which leads to the formation of larger protein complexes via the SH3 domains. Nck plays a pivotal role in T-cell receptor-mediated reorganization of the actin cytoskeleton as well as in the formation of the immunological synapses. The modular domain structure and the functionality of the individual domains suggest that they might act independently. Here we report an interesting intramolecular interaction within Nck that occurs between a noncanonical yet conserved (K/R)x(K/R)RxxS sequence in the linker between the first and second SH3 domain (SH3.1/SH3.2) and the second SH3 domain (SH3.2). Because this interaction masks the proline-rich sequence binding site of the SH3.2 domain, the intramolecular interaction is self-inhibitory. This intramolecular interaction could, at least partially, explain the remarkable specificity of Nck toward proteins with proline-rich sequences. It may prevent nonspecific low-affinity binding while keeping the site available for high-affinity bivalent ligands that can bind multiple sites in Nck. This indicates that Nck does not simply adopt a "beads on a string" architecture but incorporates a higher-order organization for improved specificity and functionality.

SUBMITTER: Takeuchi K

PROVIDER: S-EPMC2899887 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity.

Takeuchi Koh K Sun Zhen-Yu J ZY Park Sunghyouk S Wagner Gerhard G

Biochemistry 20100701 27

Nck is a functionally versatile multidomain adaptor protein consisting of one SH2 and three SH3 domains. In most cases, the SH2 domain mediates binding to tyrosine-phosphorylated receptors or cytosolic proteins, which leads to the formation of larger protein complexes via the SH3 domains. Nck plays a pivotal role in T-cell receptor-mediated reorganization of the actin cytoskeleton as well as in the formation of the immunological synapses. The modular domain structure and the functionality of the ...[more]

PMID: 20527928

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Project description:Despite the popularity of kombucha tea, the distribution of different microbes across kombucha ferments and how those microbes interact within communities are not well characterized. Using metagenomics, comparative genomics, synthetic community experiments, and metabolomics, we determined the taxonomic, ecological, and functional diversity of 23 distinct kombuchas from across the United States. Shotgun metagenomic sequencing demonstrated that the bacterium Komagataeibacter rhaeticus and the yeast Brettanomyces bruxellensis were the most common microbes in the sampled kombucha communities. To determine the specificity of bacterium-yeast interactions, we experimentally quantified microbial interactions within kombucha biofilms by measuring densities of interacting species and biofilm production. In pairwise combinations of bacteria and yeast, B. bruxellensis and individual strains of Komagataeibacter spp. were sufficient to form kombucha fermentations with robust biofilms, but Zygosaccharomyces bisporus, another yeast found in kombucha, did not stimulate bacteria to produce biofilms. Profiling the spent media of both yeast species using nuclear magnetic resonance spectroscopy suggested that the enhanced ability of B. bruxellensis to ferment and produce key metabolites in sucrose-sweetened tea may explain why it stimulates biofilm formation. Comparative genomics demonstrated that Komagataeibacter spp. with >99% genomic similarity can still have dramatic differences in biofilm production, with strong producers yielding five times more biofilm than the weakest producers. IMPORTANCE Through an integration of metagenomic and experimental approaches, our work reveals the diversity and nature of interactions among key taxa in kombucha microbiomes through the construction of synthetic microbial pairs. Manipulation of these microbes in kombucha has the potential to shape both the fermentation qualities of kombucha and the production of biofilms and is valuable for kombucha beverage producers, biofilm engineers, and synthetic ecologists.

Dataset Information

Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity.

Publications

Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity.

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