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Results for “Amino Acid Motifs”

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At least 19 recordsLinked to original sources

PubMed2025

Annotation of RxLR Effectors in Oomycete Genomes.

Pathogens have evolved effector proteins to suppress host immunity and facilitate plant infections. RxLR effectors are small, secreted effector proteins with conserved RxLR and dEER amino acid motifs at the N terminus and highly variable C termini and are commonly found in oomycete species. We provide computational approaches to annotate RxLR candidate effector genes in a genome assembly in FASTA format with an available GFF file. Hidden Markov Modeling (HHM) is used in combination with regular expressions to search for RxLR and EER amino acid patterns.

Oomycetes↗

PubMed2002

The ETS domain transcription factor Elk-1 contains a novel class of repression domain.

The ETS domain transcription factor Elk-1 serves as an integration point for different mitogen-activated protein (MAP) kinase pathways. Phosphorylation of Elk-1 by MAP kinases triggers its activation. However, while the activation process is well understood, its downregulation-inactivation is less well characterized. The ETS DNA-binding domain plays a role in the downregulation of Elk-dependent promoter activity following mitogenic activation by recruiting the mSin3A-HDAC complex. Here we have identified a novel evolutionarily conserved repression domain in Elk-1, termed the R motif, which serves to reduce the basal transcriptional activity of Elk-1 and dampen its response to mitogenic signals. This domain is highly potent and portable and can repress transcription in trans. The R motif is related to the CRD1 repression domain in p300 and can functionally replace this domain and confer p21(waf1/cip1) inducibility on p300. However, the R motif acts in a context-dependent manner and is not p21(waf1/cip1) responsive in Elk-1. Thus, the Elk-1 R motif and the p300 CRD1 motif represent a new class of repression domains that are regulated in a context-dependent manner.

Amino Acid Motifs↗

PubMed2001

Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation.

Oxygen-dependent proteolytic destruction of hypoxia-inducible factor-alpha (HIF-alpha) subunits plays a central role in regulating transcriptional responses to hypoxia. Recent studies have defined a key function for the von Hippel-Lindau tumour suppressor E3 ubiquitin ligase (VHLE3) in this process, and have defined an interaction with HIF-1 alpha that is regulated by prolyl hydroxylation. Here we show that two independent regions within the HIF-alpha oxygen-dependent degradation domain (ODDD) are targeted for ubiquitylation by VHLE3 in a manner dependent upon prolyl hydroxylation. In a series of in vitro and in vivo assays, we demonstrate the independent and non-redundant operation of each site in regulation of the HIF system. Both sites contain a common core motif, but differ both in overall sequence and in the conditions under which they bind to the VHLE3 ligase complex. The definition of two independent destruction domains implicates a more complex system of pVHL-HIF-alpha interactions, but reinforces the role of prolyl hydroxylation as an oxygen-dependent destruction signal.

Amino Acid Motifs↗

PubMed2025

Translational reading frame determines the pathogenicity of C-terminal frameshift deletions in MeCP2: an alternative therapeutic approach.

Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome. A cluster of frameshift-causing C-terminal deletions (CTDs) lead to loss of ~100 amino acids at the C-terminus of the MeCP2 protein, and account for approximately 10% of RTT-causing mutations. The pathogenicity of C-terminal deletions (CTDs) is unexpected, as this C-terminal domain is non-essential in mice. Utilising databases of pathogenic and benign human MECP2 mutations, we find that some individuals with apparently typical CTDs do not exhibit Rett syndrome, confirming that C-terminal truncations are not intrinsically pathogenic. Using human DNA sequence data and mouse models, we demonstrate that pathogenicity results from a drastic reduction in MeCP2 levels and is determined by the presence of the short amino acid motif proline-proline-stop (-PPX) at the C-terminus, which results from a shift to the +2 reading frame. Individuals with CTDs that shift to the +1 frame avoid this motif and do not develop Rett syndrome. Mutating the stop codon of the PPX motif to tryptophan rescues MeCP2 expression and RTT-like phenotypes in a CTD mouse model. Finally, we demonstrate that an adenine base editor can efficiently introduce this tryptophan substitution in cultured cells. Overall, our findings uncover a simple and reliable prognostic distinction between benign and pathogenic CTDs and provide proof-of-concept for an editing strategy that potentially corrects all disease-causing CTD mutations.

Journal Article↗

PubMed2026

Shared CD4+ T cell receptor specificity groups in Crohn's disease and ulcerative colitis.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is marked by chronic intestinal inflammation and dysregulated immunity. Although UC and CD affect different areas of the gastrointestinal tract, both diseases share aberrant CD4+ memory T cell responses, with HLA-DRB1 as a major genetic risk factor. HLA-DRB1 encodes MHC class II molecules that influence the CD4+ T cell receptor (TCR) repertoire, yet how these genotypes shape TCR specificity in IBD remains unclear. Here, we genotyped HLA-DRB1 and profiled 3.13 million TCRβ sequences from circulating memory CD4+ T cells in 33 IBD patients (20 UC, 13 CD) and 14 healthy controls. Using the GLIPH2 algorithm, we distilled 468,441 candidates based on CDR3 amino acid motifs into 440 high-confidence TCR specificity groups significantly enriched among individuals sharing HLA-DRB1 alleles. Notably, 5 specificity groups were IBD-enriched and were shared between UC and CD, suggesting common antigen targets in both diseases. We also observed increased frequencies of clonally expanded cytotoxic GZMB+PRF1+ memory CD4+ T cells and KIR+CD8+ T cells in a subset of risk-allele carriers with IBD. These findings elucidate distinct, HLA-linked TCR specificity groups in IBD and provide mechanistic insights that may advance antigen discovery and personalized medicine.

Humans↗

PubMed2025

Integrating AlphaFold2 models and clinical data to improve the assessment of Short Linear Motifs (SLiMs) and their variants' pathogenicity.

Short Linear Motifs (SLiMs) are protein functionally relevant regions that mediate reversible protein-protein interactions. Variants that disrupt SLiMs can lead to numerous Mendelian diseases. Although various bioinformatic tools have been developed to identify SLiMs, most suffer from low specificity. In our previous work, we demonstrated that integrating sequence variant information with structural analysis can enhance the prediction of true functional SLiMs while simultaneously generating tolerance matrices that indicate whether each of the 19 possible single amino acid substitutions (SASs) is tolerated. However, the scarcity of representative crystallographic structures of SLiM-receptor complexes posed a significant limitation. In this study, we demonstrate that these interactions can be modeled using AlphaFold2 (AF2) to generate high-quality structures that serve as input for our MotSASi method. These AF2-derived structures show robust performance, both in reproducing known structures deposited in the Protein Data Bank (PDB) and in reflecting the deleterious effects of known sequence variants. This updated version of MotSASi expands the repertoire of high-confidence predicted SLiMs and provides a comprehensive catalog of variants located within SLiMs, along with their respective deleteriousness assessments. When compared to AlphaMissense, MotSASi demonstrates superior performance in predicting variant deleteriousness. By contributing to the accurate identification and interpretation of variants, this work aligns with ACMG/AMP standards and aims to improve diagnostic rates in clinical genomics.

Humans↗

PubMed2026

Disruption of GxxxG motifs in pATOM36 impairs biogenesis of the mitochondrial protein translocase of the outer membrane in Trypanosoma brucei.

Mitochondrial biogenesis requires efficient import of cytosolically produced proteins and correct segregation of the mitochondrial genome during cytokinesis. In Trypanosoma brucei, a parasitic protozoan with a single mitochondrion harboring a single-unit mitochondrial genome, protein import across the outer membrane is mediated by the ATOM complex. An important, yet poorly understood role is played by the integral membrane protein pATOM36 of the outer mitochondrial membrane, which is essential for both ATOM complex assembly and mitochondrial DNA segregation. Here, we combined in vivo functional mutational analysis and structural modeling to investigate the function of pATOM36. AlphaFold3-based models predict five highly tilted helices forming a funnel-shaped cavity open toward the cytoplasm, reminiscent of membrane protein insertases. In the model, the protein is sealed towards the mitochondrial intermembrane space by tight helix packing, with conserved GxxxG motifs potentially facilitating these helix-helix interactions. Progressive replacement of these glycines by isoleucines does not affect protein production or correct localization but leads to defective ATOM complex biogenesis and arrest of growth, while mitochondrial DNA segregation is largely unaffected. Based on the predicted structure, these effects can be rationalized by hydrophobic bulking that interferes with associated electrostatic interactions. This hypothesis is supported by experimental mutational analysis of the respective electrostatic interactions in the presence of native GxxxG motifs. Together, our data support the hypothesis that pATOM36 functions as an outer mitochondrial insertase and arose by convergent evolution. The GxxxG motifs, also found in unrelated yeast and human outer membrane insertases, are crucial for protein activity.

Trypanosoma brucei brucei↗

PubMed2004

Single nucleotide polymorphism-based validation of exonic splicing enhancers.

Because deleterious alleles arising from mutation are filtered by natural selection, mutations that create such alleles will be underrepresented in the set of common genetic variation existing in a population at any given time. Here, we describe an approach based on this idea called VERIFY (variant elimination reinforces functionality), which can be used to assess the extent of natural selection acting on an oligonucleotide motif or set of motifs predicted to have biological activity. As an application of this approach, we analyzed a set of 238 hexanucleotides previously predicted to have exonic splicing enhancer (ESE) activity in human exons using the relative enhancer and silencer classification by unanimous enrichment (RESCUE)-ESE method. Aligning the single nucleotide polymorphisms (SNPs) from the public human SNP database to the chimpanzee genome allowed inference of the direction of the mutations that created present-day SNPs. Analyzing the set of SNPs that overlap RESCUE-ESE hexamers, we conclude that nearly one-fifth of the mutations that disrupt predicted ESEs have been eliminated by natural selection (odds ratio = 0.82 +/- 0.05). This selection is strongest for the predicted ESEs that are located near splice sites. Our results demonstrate a novel approach for quantifying the extent of natural selection acting on candidate functional motifs and also suggest certain features of mutations/SNPs, such as proximity to the splice site and disruption or alteration of predicted ESEs, that should be useful in identifying variants that might cause a biological phenotype.

Alleles↗

PubMed2026

Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles.

Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds predisposed to immune-mediated diseases. Because dogs co-express DLA-DR and DLA-DQ, the MHC class II Ab clone YKIX334.2 was validated to be DLA-DR-specific, enabling allele-selective immunoaffinity purification of DLA-DR molecules from homozygous DLA-DR15 and DLA-DR12 donor spleens. Mass spectrometry and GibbsCluster motif deconvolution of 838 DLA-DR15-associated and 644 DLA-DR12-associated peptides eluted from their respective peptide-binding grooves revealed distinct allele-specific binding motifs, with characterization of anchor residue preferences, peptide-length distributions, cross-species comparisons with human and murine MHC class II motifs, and source protein composition of the eluted self-peptidome. To evaluate the translational utility of these motifs, recombinant DLA-DR15 and DLA-DR12 molecules were used to screen rabies virus glycoprotein and nucleoprotein peptide libraries via fluorescence-based peptide competition assays, identifying high-affinity candidate binders for both alleles. Spearman rank correlation between immunopeptidomics-derived position-specific scoring matrix scores and peptide competition assay rankings demonstrated modest associations, consistent with these approaches capturing complementary dimensions of peptide-MHC class II interaction. Ultimately, these findings establish what we believe is the first allele-specific peptide-binding motif framework for canine MHC class II, providing a foundation for DLA-allele-informed CD4+ T-cell epitope discovery studies and Ag-specific immune response characterization in the dog.

Animals↗

PubMed2025

MAFin: motif detection in multiple alignment files.

MOTIVATION: Whole Genome and Proteome Alignments, represented by the multiple alignment file format, have become a standard approach in comparative genomics and proteomics. These often require identifying conserved motifs, which is crucial for understanding functional and evolutionary relationships. However, current approaches lack a direct method for motif detection within MAF files. We present MAFin, a novel tool that enables efficient motif detection and conservation analysis in MAF files to address this gap, streamlining genomic and proteomic research. RESULTS: We developed MAFin, the first motif detection tool for Multiple Alignment Format files. MAFin enables the multithreaded search of conserved motifs using three approaches: (i) using user-specified k-mers to search the sequences. (ii) with regular expressions, in which case one or more patterns are searched, and (iii) with predefined Position Weight Matrices. Once the motif has been found, MAFin detects the motif instances and calculates the conservation across the aligned sequences. MAFin also calculates a conservation percentage, which provides information about the conservation levels of each motif across the aligned sequences, based on the number of matches relative to the length of the motif. A set of statistics enables the interpretation of each motif's conservation level, and the detected motifs are exported in JSON and CSV files for downstream analyses. AVAILABILITY AND IMPLEMENTATION: MAFin is offered as a Python package under the GPL license as a multi-platform application and is available at: https://github.com/Georgakopoulos-Soares-lab/MAFin.

Software↗

PubMed2025

Harnessing deep learning for proteome-scale detection of amyloid signaling motifs.

MOTIVATION: Amyloid signaling sequences adopt the cross-β fold that is capable of self-replication in the templating process. Propagation of the amyloid fold from the receptor to the effector protein is used for signal transduction in the immune response pathways in animals, fungi, and bacteria. So far, a dozen of families of amyloid signaling motifs (ASMs) have been classified. Unfortunately, due to the wide variety of ASMs it is difficult to identify them in large protein databases available, which limits the possibility of conducting experimental studies. To date, various deep learning (DL) models have been applied across a range of protein-related tasks, including domain family classification and the prediction of protein structure and protein-protein interactions. RESULTS: In this study, we develop tailor-made bidirectional LSTM and BERT-based architectures to model ASM, and compare their performance against a state-of-the-art machine learning grammatical model. Our research is focused on developing a discriminative model of generalized ASMs, capable of detecting ASMs in large datasets. The DL-based models are trained on a diverse set of motif families and a global negative set, and used to identify ASMs from remotely related families. We analyze how both models represent the data and demonstrate that the DL-based approaches effectively detect ASMs, including novel motifs, even at the genome scale. AVAILABILITY AND IMPLEMENTATION: The models are provided as a Python package, asmscan-bilstm, and a Docker image at https://github.com/chrispysz/asmscan-proteinbert-run. The source code can be accessed at https://github.com/jakub-galazka/asmscan-bilstm and https://github.com/chrispysz/asmscan-proteinbert. Data and results are at https://github.com/wdyrka-pwr/ASMscan.

Deep Learning↗

PubMed2025

Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and MIB2-mediated signaling.

Ebola virus (EBOV) is a nonsegmented, negative-sense virus (NNSV) with a single-stranded RNA genome. EBOV encodes for a limited number of proteins and thus depends on host factors to facilitate viral replication and pathogenesis. Of the virus-encoded proteins, multifunctional EBOV VP35 (eVP35) is necessary for host immune evasion and viral RNA synthesis. Previous proteomics studies identified an interaction between eVP35 and the host E3 ubiquitin ligase Mindbomb 2 (MIB2). Here, we show how an NNLNS (Asn-Asn-Leu-Asn-Ser) motif (residues 201 to 205) within eVP35 serves as a binding site for MIB2. This motif is critical for eVP35-dependent inhibition of MIB2-mediated interferon induction. It is also important for EBOV RNA synthesis as MIB2 binding to eVP35 inhibited EBOV minigenome activity. Altogether, these findings highlight the importance of the eVP35 protein and the role of host factors in EBOV infection.

Ebolavirus↗

PubMed2026

Molecular basis of collagen triple helix recognition by VWF A-like domain two of collagen VII: Implications for interlaced anchoring fibril formation.

Anchoring fibrils formed by collagen VII play a critical role in stabilizing the dermal-epidermal junction. The N-terminal non-collagenous (NC1) domain of collagen VII binds firmly to basement membrane components including collagen IV and has also been reported to interact with mesenchymal fibrillar collagens via its von Willebrand factor A-like domain 2 (A2 domain). To elucidate how collagen VII recognizes fibrillar collagen, we performed yeast two-hybrid screening using a triple-helical random peptide library, which resulted in the identification of a Met-Gly-Φ (Φ; aromatic amino acid residue) motif. Biochemical analysis with synthetic triple-helical peptides revealed a binding preference of Trp > Phe as the Φ residue by the A2 domain despite Trp being absent in native collagens. The crystal structure of the A2 domain in complex with the Nle (Met surrogate)-Gly-Trp-containing peptide revealed a unique mechanism by which two distinct hydrophobic pockets of the A2 domain accommodate the Nle and Trp residues corresponding to the Met-Gly-Φ motif, engaging all three chains of the triple helix. Subsequent molecular dynamics simulations demonstrated that the A2 domain recognizes the corresponding native Met-Gly-Phe motif in a similar manner, but with lower affinity, implying a transient interaction with mesenchymal collagens. The findings obtained in this work suggest models in which transient A2-triple helix interaction promotes the recruitment of collagen I and III fibrils into the arc-shaped structure of anchoring fibrils. This also provides a foundation for linking structural understanding to skin fragility diseases caused by collagen VII dysfunction.

anchoring fibril↗

PubMed2015

Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia.

B cells are selected for an intermediate level of B-cell antigen receptor (BCR) signalling strength: attenuation below minimum (for example, non-functional BCR) or hyperactivation above maximum (for example, self-reactive BCR) thresholds of signalling strength causes negative selection. In ∼25% of cases, acute lymphoblastic leukaemia (ALL) cells carry the oncogenic BCR-ABL1 tyrosine kinase (Philadelphia chromosome positive), which mimics constitutively active pre-BCR signalling. Current therapeutic approaches are largely focused on the development of more potent tyrosine kinase inhibitors to suppress oncogenic signalling below a minimum threshold for survival. We tested the hypothesis that targeted hyperactivation--above a maximum threshold--will engage a deletional checkpoint for removal of self-reactive B cells and selectively kill ALL cells. Here we find, by testing various components of proximal pre-BCR signalling in mouse BCR-ABL1 cells, that an incremental increase of Syk tyrosine kinase activity was required and sufficient to induce cell death. Hyperactive Syk was functionally equivalent to acute activation of a self-reactive BCR on ALL cells. Despite oncogenic transformation, this basic mechanism of negative selection was still functional in ALL cells. Unlike normal pre-B cells, patient-derived ALL cells express the inhibitory receptors PECAM1, CD300A and LAIR1 at high levels. Genetic studies revealed that Pecam1, Cd300a and Lair1 are critical to calibrate oncogenic signalling strength through recruitment of the inhibitory phosphatases Ptpn6 (ref. 7) and Inpp5d (ref. 8). Using a novel small-molecule inhibitor of INPP5D (also known as SHIP1), we demonstrated that pharmacological hyperactivation of SYK and engagement of negative B-cell selection represents a promising new strategy to overcome drug resistance in human ALL.

Amino Acid Motifs↗

PubMed2026

GAMMA: gap-aware motif mining under incomplete labeling with applications to MHC motifs.

MOTIVATION: Sequence motif identification is crucial for understanding molecular recognition, particularly in immune responses involving peptide binding to major histocompatibility complex (MHC) Class I molecules for antigen presentation to T cells. Traditionally, MHC Class I binding motifs are assumed to be contiguous and span nine amino acids. However, structural evidence suggests that binding may involve nonadjacent residues, challenging the assumptions of existing methods. RESULTS: In this study, we propose Gap-Aware Motif Mining Algorithm (GAMMA), a probabilistic framework designed to identify noncontiguous motifs under conditions of incomplete labeling. GAMMA employs Bayesian inference with Markov chain Monte Carlo sampling to jointly estimate motif parameters, binding locations, and the relative spacing between binding positions. Through extensive simulations and real-world applications to MHC Class I peptide datasets, GAMMA outperforms existing motif discovery tools such as GLAM2 in accurately localizing binding residues and identifying the underlying motifs. Notably, our results suggest that the true number of binding residues may be eight, fewer than the commonly assumed nine. In addition, for longer peptides, the model captures increased flexibility in the central region, consistent with structural observations that peptides may bulge in the middle. AVAILABILITY AND IMPLEMENTATION: The raw data and the source codes are available on GitHub (https://github.com/RanLIUaca/GAMMAmotif).

Amino Acid Motifs↗

PubMed2026

Characterization of a Ku-binding motif in the C-terminal region of RAG2.

We applied an unsupervised interactome analysis with the RAG2 C-terminal region (R2CT) in v-abl pro-B cells undergoing V(D)J recombination. Mass-spectrometry analyses showed that Ku70 and Ku80 were among the top 10 hits. To further strengthen these observations, we performed Proximity Ligation Assay (PLA) and characterize the existence of a GFP-R2CT-Ku complex formation in cellulo. The interaction of several partners with Ku70/80 (Ku) through Ku-binding motifs (KBMs) in their sequences governs their enrolment in NHEJ repair complexes. Through sequence analysis, we identified a KBM within R2CT (R-KBM, amino acids 589-527). We confirmed by calorimetry a specific micromolar interaction between this RAG2 region and Ku70/80/DNA complex. The RAG2 motif KBM can be subdivided in two conserved parts that have no interaction individually. AlphaFold2 prediction coupled with molecular dynamic simulations indicate that the C-terminal part of the RAG2 motif interacts with Ku80 on the same site than the NHEJ factor XLF. These in silico analyses indicated that the N-terminal part of the RAG2 motif interacts with DNA adjacent to Ku with a major role of the K503 residue in agreement with disruption of the interaction observed with the K503E mutant. This study further extends the large ensemble of proteins recruited at DSBs by KBM motifs and substantiates the model of a tight coupling between DNA breakage and repair during V(D)J recombination, mediated by the Ku-RAG2 C-terminus interaction.

Ku Autoantigen↗

PubMed2026

Positional grammar of transcription factor binding partitions developmental and stress-response regulation in plants.

Understanding how transcription factor binding site (TFBS) position influences gene regulation remains a fundamental challenge in plants. Here, we integrate conserved multiDAP TFBS maps for 244 transcription factors (TFs) with single-nucleus chromatin accessibility, cell type-resolved gene expression, and hormone-response datasets across Brassicaceae species to determine how TFBS position relates to regulatory function. Although conserved TFBSs are enriched near transcription start sites (TSSs), TSS-proximal accessibility poorly predicts cell type-specific expression. Instead, cell type-specific expression correlates best with conserved TFBSs embedded in cell type-restricted chromatin, with TF family-specific distributions across distal promoters and introns. In contrast, TSS-proximal TFBSs in broadly accessible chromatin are associated with rapid transcriptional responses to abiotic and biotic stress hormones. Coding sequence TFBSs mark a distinct regulatory context in which the same DNA sequence encodes both amino acid sequence and TF motifs, including evidence that CDS-localized ABR1 binding may contribute to repression during hormone response. Finally, distal upstream regions contain conserved multi-family TF clusters with enhancer-like features overlapping rare cell type-specific accessible chromatin and enriched near genes controlling embryonic, meristematic, and hormone-dependent developmental patterning. Together, these results support a positional grammar in which TFBS position and chromatin context jointly partition developmental, stress-responsive, and repressive regulatory output in plants.

Transcription Factors↗

PubMed2026

Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency.

Viral 2A oligopeptides drive an unusual ribosome recoding event in which peptide-bond formation fails at a conserved PG↓P motif, producing two discrete proteins without canonical termination. Despite decades of study, the molecular basis of 2A-mediated peptide-bond skipping remains poorly understood. Here, we combine quantitative 2A reporters with high-resolution ribosome profiling to interrogate ribosome dynamics at the core 2A sequences. We identify a pausing event at the terminal proline codon of the PGP motif that functions as a kinetic decision point: ribosome dwell time at this site inversely correlates with skipping efficiency. Increasing nascent chain flexibility by inserting linkers immediately upstream of the 2A sequence reduces ribosome occupancy at the terminal proline codon and enhances peptide-bond skipping. Strikingly, amino acid repeats positioned distally upstream also modulate 2A activity, indicating long-range coupling between nascent chain properties outside of the ribosome and the peptidyl transferase center inside the ribosome. In particular, hydrophobic residues potently suppress skipping, an effect that can be rescued by extending flexible segments within the peptide exit tunnel. Together, our findings support a model in which nascent chain features-beyond the core 2A motif-dynamically tune ribosomal recoding efficiency through co-translational feedback into the catalytic center.

Ribosomes↗