Dual Role of Entamoeba histolytica KERP2 in Regulating Gene Expression and Modulating Host Cell Function for Intestinal Colonization DOI
Tomoyoshi Nozaki, Ruofan Peng, Herbert Santos

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Entamoeba histolytica, the protozoan parasite responsible for amoebiasis, deploys a complex array of virulence factors to establish infection and evade host defenses. Here, we identify KERP2 as dual-function effector that regulates both homeostasis cell remodeling. Bioinformatic analyses, cellular localization assays, functional studies show localizes nucleus, associates with chromatin, modulates transcription, particularly regulating cysteine protease expression sulfur metabolism. Concurrently, is translocated into epithelial cells, where it manipulates G1/S transition, interacts cytoskeletal regulators, promotes actin remodeling, ultimately compromising barrier function. Our results elucidate how E. histolytica harnesses coordinate intracellular processes in while orchestrating pathogenic alterations cells. These insights shed light on broader mechanism by which extracellular pathogens deploy multifunctional effectors optimize adapt diverse environments, providing valuable framework pathogen-host interactions beyond amoebiasis.

Language: Английский

Determining the Role of OsAGP6P in Anther Development Within the Arabinogalactan Peptide Family of Rice (Oryza sativa) DOI Open Access
Shuai Shao, Yuxin Wu, Lijie Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2616 - 2616

Published: March 14, 2025

Arabinogalactan proteins (AGPs) are complex proteoglycans present in plant cell walls across the kingdom. They play crucial roles biological functions throughout life cycle. In this study, we identified 43 gene members of AG peptide (an AGP subfamily) within rice genome, detailing their structure, protein-conserved domains, and motif compositions for first time. We also examined expression patterns these genes 18 tissues organs, especially different parts flower (anthers, pollen, pistil, sperm cells, egg cells). Interestingly, some peptides is mainly pollen grain. Transcription data GUS staining confirmed that OsAGP6P—a member family—is expressed stamen during development stages 11–14, which critical maturation as microspores form after meiosis mother cells. It became noticeable from stage 11, when exine formation occurred—specifically at 12, intine began to develop. The overexpression decreased seed-setting rate (from 91.5% 30.5%) height (by 21.9%) but increased tillering number 34.1%). These results indicate AGP6P contributes fertility making it a valuable target future genetic manipulation sterility through or editing.

Language: Английский

Citations

0

Rational Design Principles for De Novo α-Helical Peptide Barrels with Dynamic Conductive Channels DOI

Ai Niitsu,

Andrew R. Thomson,

Alistair J. Scott

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Despite advances in peptide and protein design, the rational design of membrane-spanning peptides that form conducting channels remains challenging due to our imperfect understanding sequence-to-structure relationships drive membrane insertion, assembly, conductance. Here, we describe computational experimental characterization a series coiled coil-based transmembrane α-helical barrels with conductive channels. Through combination obtain 5 7 helices, as characterized detergent micelles. In lipid bilayers, these assemblies exhibit two conductance states relative populations dependent on applied potential: (i) low-conductance correlate variations designed amino-acid sequences modeled coiled-coil barrel geometries, indicating stable barrels; (ii) high-conductance which single change size discrete steps. Notably, are similar for all contrast states. This indicates formation large, dynamic channels, observed natural barrel-stave These findings establish routes tune functional specific geometry.

Language: Английский

Citations

0

Proteomimetic Strategy for the Modulation of Intrinsically Disordered Protein MYC DOI Creative Commons
Thu Trang Nguyễn, Seong Ho Hong, Paramjit S. Arora

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

The difficulty in developing specific ligands for protein receptors is directly correlated to the presence of unique binding sites on surface. Conformationally dynamic proteins increase level ligand design, and challenge further exacerbated that are intrinsically disordered. Intrinsically disordered (or IDPs) do not adopt a fixed three-dimensional shape until they bind their target; an absence organized underscores synthetic these proteins. We hypothesized one avenue development binders region would be trap its thermodynamically accessible conformations receptor. Here, we show application this approach MYC, which represents critical therapeutic target but has yielded small-molecule inhibitors due conformationally nature. MYC adopts helical configuration when it binds cellular partner MAX. rationally designed proteomimetic scaffold conformation. can engaged both biochemical assays. Overall, work demonstrates general method capture with propensity α-helical conformations.

Language: Английский

Citations

0

De Novo Design of Parallel and Antiparallel A3B3 Heterohexameric α-Helical Barrels DOI Creative Commons
J Chubb, Katherine I. Albanese, Alison Rodger

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

The de novo design of α-helical coiled-coil peptides is advanced. Using established sequence-to-structure relationships, it possible to generate various assemblies with predictable numbers and orientations helices. Here, we target new assemblies, namely, A3B3 heterohexamer barrels. These designs are based on pairs sequences three heptad repeats (abcdefg), programmed a = Leu, d Ile, e Ala, g Ser, b c Glu make the acidic (A) chains Lys in basic (B) chains. rules ensure that desired oligomeric state stoichiometry readily achieved. However, controlling orientation neighboring helices (parallel or antiparallel) less straightforward. Surprisingly, find assembly helix sensitive length overhang between To study this, cyclically permutated peptide (the register) were analyzed. Peptides starting at (g-register) form parallel 6-helix barrel solution an X-ray crystal structure, whereas b- c-register antiparallel complex. In lieu experimental structures for peptides, AlphaFold-Multimer used predict atomistic models. considerably more sampling than default value required match models data, as many confidently predicted plausible generated incorrect orientations. This work reveals previously unknown influence register helical provides insights modeling oligopeptide complexes AlphaFold.

Language: Английский

Citations

0

Dual Role of Entamoeba histolytica KERP2 in Regulating Gene Expression and Modulating Host Cell Function for Intestinal Colonization DOI
Tomoyoshi Nozaki, Ruofan Peng, Herbert Santos

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Entamoeba histolytica, the protozoan parasite responsible for amoebiasis, deploys a complex array of virulence factors to establish infection and evade host defenses. Here, we identify KERP2 as dual-function effector that regulates both homeostasis cell remodeling. Bioinformatic analyses, cellular localization assays, functional studies show localizes nucleus, associates with chromatin, modulates transcription, particularly regulating cysteine protease expression sulfur metabolism. Concurrently, is translocated into epithelial cells, where it manipulates G1/S transition, interacts cytoskeletal regulators, promotes actin remodeling, ultimately compromising barrier function. Our results elucidate how E. histolytica harnesses coordinate intracellular processes in while orchestrating pathogenic alterations cells. These insights shed light on broader mechanism by which extracellular pathogens deploy multifunctional effectors optimize adapt diverse environments, providing valuable framework pathogen-host interactions beyond amoebiasis.

Language: Английский

Citations

0