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The M13 tip protein, g3p, binds the C-terminal domain of the bacterial membrane protein TolA via β-sheet augmentation, facilitating viral entry into E. coli. G3p binding leads to rearrangement of the β strands and partial unfolding of TolA. G3p also binds multiple amyloid assemblies with high affinity, and it can remodel them into amorphous aggregates. We previously showed that amyloid binding activity is defined by the two g3p N-terminal domains, which we call the General Amyloid Interaction Motif (GAIM). GAIM-hIgG1Fc fusions, which add immune effector function to amyloid targeting of GAIM, mediate reduction of two CNS amyloid deposits, Aβ plaques and tau tangles, in transgenic animal models of neurodegenerative disease. We carried out site-directed mutagenesis of GAIM to identify variants with altered amyloid binding and remodeling activity. A small set of residues along the inner strands of the two domains regulates both activities. The specificity of amyloid binding is governed by individual domain stability and inter-domain interactions. Our studies reveal several lines of similarity between GAIM binding to amyloids and g3p binding to its E. coli membrane target, TolA. Based on these studies, we designed new GAIM fusions which show enhanced binding potency towards multiple amyloid aggregates.
This article was published in the following journal.
Name: Journal of molecular biology
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A type of extracellularly deposited substance composed of an amyloid protein and additional components including HEPARAN SULFATE PROTEOGLYCAN; LAMININ; COLLAGEN TYPE IV; SERUM AMYLOID P-COMPONENT; and APOLIPOPROTEINS E which together form characteristic amyloid fibrils. The core of amyloid fibrils is formed by the stacking of overlapping beta-pleated sheet domains of the amyloid protein. There are many different amyloid proteins that have been found forming the core of the fibrils in vivo. However, amyloid can be formed from any protein that exposes beta-pleated strand conformations during unfolding or refolding. A common characteristic of amyloid is the ability to bind such dyes as CONGO RED and thioflavine.
The inter- and intra-relationships between various microorganisms. This can include both positive (like SYMBIOSIS) and negative (like ANTIBIOSIS) interactions. Examples include virus - bacteria and bacteria - bacteria.
A syndecan that is predominantly expressed during EMBRYONIC DEVELOPMENT. It may play a role in mediating cellular interactions with the EXTRACELLULAR MATRIX and may modulate the signaling activity of certain INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
A family of transcription factors characterized by the presence of a bipartite DNA-binding domain known as the POU domain. The POU domain contains two subdomains, a POU-specific domain and a POU-homeodomain. The POU domain was originally identified as a region of approximately 150 amino acids shared between the Pit-1, Oct-1, Oct-2, and Unc-86 transcription factors.
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