Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to the regulation of homeostasis. We ...have shown that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. A label-free quantitative proteomics approach revealed that Bcl-G may contribute to the stability of a mucin network, which when disrupted, is linked to colon tumorigenesis. Consistent with this, we observed a significant reduction in Bcl-G expression in human colorectal tumors. Our study identifies an unappreciated role for Bcl-G in colon cancer.
Many proteins involved in signal transduction contain peptide recognition modules (PRMs) that recognize short linear motifs (SLiMs) within their interaction partners. Here, we used large‐scale ...peptide‐phage display methods to derive optimal ligands for 163 unique PRMs representing 79 distinct structural families. We combined the new data with previous data that we collected for the large SH3, PDZ, and WW domain families to assemble a database containing 7,984 unique peptide ligands for 500 PRMs representing 82 structural families. For 74 PRMs, we acquired enough new data to map the specificity profiles in detail and derived position weight matrices and binding specificity logos based on multiple peptide ligands. These analyses showed that optimal peptide ligands resembled peptides observed in existing structures of PRM‐ligand complexes, indicating that a large majority of the phage‐derived peptides are likely to target natural peptide‐binding sites and could thus act as inhibitors of natural protein–protein interactions. The complete dataset has been assembled in an online database (http://www.prm‐db.org) that will enable many structural, functional, and biological studies of PRMs and SLiMs.
SYNOPSIS
A database of thousands of peptides targeting hundreds of diverse peptide recognition modules is presented (www.prm‐db.org). Applications of this large dataset include exploring natural protein‐protein interactions and inhibitor design.
The database contains 7,984 unique peptides, each binding to one of 500 peptide recognition modules (PRMs) representing 82 distinct structural families.
Phage‐derived peptides reflect the hydrophobic character of natural peptides at specific positions critical for PRM recognition.
Comparative structural analysis highlights the functional importance of specific positions in peptide binding profiles.
Phage‐derived peptides resemble natural short linear motifs (SLiMs) and likely bind to the same sites.
A database of thousands of peptides targeting hundreds of diverse peptide recognition modules is presented (www.prm‐db.org). Applications of this large dataset include exploring natural protein‐protein interactions and inhibitor design.
The
etinoic acid-
nducible
ene-
(RIG-I) receptor recognizes short 5'-di- and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as ...influenza A, Ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the
partite
otif 25 (TRIM25) B30.2 protein-interaction domain. Here, we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 (
aspase
ctivation and
ecruitment
omains) of RIG-I and is revealed by the removal of an N-terminal α-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members.
Towards a Unifying Framework for Formal Theories of Novelty Boult, Terrance; Grabowicz, Przemyslaw; Prijatelj, Derek ...
Proceedings of the ... AAAI Conference on Artificial Intelligence,
05/2021, Letnik:
35, Številka:
17
Journal Article
Managing inputs that are novel, unknown, or out-of-distribution is critical as an agent moves from the lab to the open world. Novelty-related problems include being tolerant to novel perturbations of ...the normal input, detecting when the input includes novel items, and adapting to novel inputs. While significant research has been undertaken in these areas, a noticeable gap exists in the lack of a formalized definition of novelty that transcends problem domains. As a team of researchers spanning multiple research groups and different domains, we have seen, first hand, the difficulties that arise from ill-specified novelty problems, as well as inconsistent definitions and terminology. Therefore, we present the first unified framework for formal theories of novelty and use the framework to formally define a family of novelty types. Our framework can be applied across a wide range of domains, from symbolic AI to reinforcement learning, and beyond to open world image recognition. Thus, it can be used to help kick-start new research efforts and accelerate ongoing work on these important novelty-related problems.
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