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Peter C. Fridy

Bio: Peter C. Fridy is an academic researcher from Rockefeller University. The author has contributed to research in topics: Inositol & Inositol phosphate. The author has an hindex of 10, co-authored 14 publications receiving 1019 citations. Previous affiliations of Peter C. Fridy include Duke University & Howard Hughes Medical Institute.

Papers
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Journal ArticleDOI
TL;DR: The approach presented here is well suited for the routine production of high-affinity capture reagents for various biomedical applications and generates large repertoires of readily expressible recombinant nanobodies with high affinities and specificities against a given antigen.
Abstract: Nanobodies are single-domain antibodies derived from the variable regions of Camelidae atypical immunoglobulins. They show promise as high-affinity reagents for research, diagnostics and therapeutics owing to their high specificity, small size (∼15 kDa) and straightforward bacterial expression. However, identification of repertoires with sufficiently high affinity has proven time consuming and difficult, hampering nanobody implementation. Our approach generates large repertoires of readily expressible recombinant nanobodies with high affinities and specificities against a given antigen. We demonstrate the efficacy of this approach through the production of large repertoires of nanobodies against two antigens, GFP and mCherry, with Kd values into the subnanomolar range. After mapping diverse epitopes on GFP, we were also able to design ultrahigh-affinity dimeric nanobodies with Kd values as low as ∼30 pM. The approach presented here is well suited for the routine production of high-affinity capture reagents for various biomedical applications.

377 citations

Journal ArticleDOI
06 Apr 2007-Science
TL;DR: A previously uncharacterized class of inositol pyrophosphate synthase is reported and it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes.
Abstract: Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6.

249 citations

Journal ArticleDOI
TL;DR: Using cross-linking mass spectrometry, distance restraints were extracted that allowed us to model the complexes' molecular architectures and present a strategy for isolating complexes at endogenous levels from GFP-tagged transgenic cell lines.
Abstract: It remains particularly problematic to define the structures of native macromolecular assemblies, which are often of low abundance. Here we present a strategy for isolating complexes at endogenous levels from GFP-tagged transgenic cell lines. Using cross-linking mass spectrometry, we extracted distance restraints that allowed us to model the complexes' molecular architectures.

130 citations

Journal ArticleDOI
TL;DR: This study deployed a microscale metal dye detection protocol coupled to a high performance liquid chromatography system that was calibrated with synthetic and biologically synthesized standards of inositol pyrophosphates, and unequivocally determined that 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals.

127 citations

Journal ArticleDOI
TL;DR: It is demonstrated that human VIP1 and VIP2 function as IP6 and IP7 kinases that act along with the IP6K/Kcs1-class of kinases to convert IP6 to IP8 in mammalian cells, a process that has been found to occur in response to various stimuli and signaling events.

116 citations


Cited by
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01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
15 Sep 2016-Nature
TL;DR: Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.
Abstract: Numerous biological processes are concurrently and coordinately active in every living cell. Each of them encompasses synthetic, catalytic and regulatory functions that are, almost always, carried out by proteins organized further into higher-order structures and networks. For decades, the structures and functions of selected proteins have been studied using biochemical and biophysical methods. However, the properties and behaviour of the proteome as an integrated system have largely remained elusive. Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.

1,458 citations

Journal ArticleDOI
11 Feb 2016-Cell
TL;DR: A combinatorially activated T cell circuit in which a synthetic Notch receptor for one antigen induces the expression of a CAR for a second antigen opens the door to immune recognition of a wider range of tumors.

712 citations

Journal ArticleDOI
11 Feb 2016-Cell
TL;DR: It is found that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways.

639 citations

Journal ArticleDOI
TL;DR: Regulation of the Aux/IAA protein family by TIR1 and T IR1-like auxin receptors (AFBs) links auxin action to transcriptional regulation and provides a model by which the vast array of auxin influences on development may be understood.
Abstract: The plant hormone auxin, in particular indole-3-acetic acid (IAA), is a key regulator of virtually every aspect of plant growth and development. Auxin regulates transcription by rapidly modulating levels of Aux/IAA proteins throughout development. Recent studies demonstrate that auxin perception occurs through a novel mechanism. Auxin binds to TIR1, the F-box subunit of the ubiquitin ligase complex SCF TIR1 , and stabilizes the interaction between TIR1 and Aux/IAA substrates. This interaction results in Aux/IAA ubiquitination and subsequent degrada- tion. Regulation of the Aux/IAA protein family by TIR1 and TIR1-like auxin receptors (AFBs) links auxin action to transcriptional regulation and provides a model by which the vast array of auxin influences on de- velopment may be understood. Moreover, auxin receptor function is the first example of small-molecule regulation of an SCF ubiquitin ligase and may have important implications for studies of regulated protein degradation in other species, including animals.

578 citations