Video Experimental Relacionado
Updated: May 18, 2026
08:23
De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
La minería del metagenoma revela las politeonamidas como péptidos ribosómicos modificados post-traduccionalmente
Michael F Freeman1, Cristian Gurgui, Maximilian J Helf
1Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Science (New York, N.Y.)
|September 18, 2012
Resumen
Este estudio revela que las toxinas de las esponjas marinas son sintetizadas ribosomalmente por bacterias, desafiando el paradigma de sólo los ácidos l-amino en los productos ribosómicos. Estas toxinas funcionan como potentes canales de iones unimoleculares.
Área de la Ciencia:
- Bioquímica y Biología Molecular.
- Química de Productos Naturales Química de Productos Naturales
- Biología Marina Biología Marina.
Sus antecedentes:
- El paradigma prevaleciente establece que los péptidos y proteínas sintetizados ribosomalmente incorporan exclusivamente ácidos l-amino.
- Las politeonamidas derivadas de las esponjas marinas son potentes toxinas de productos naturales con estructuras complejas.
- Las vías biosintéticas para tales productos naturales complejos a menudo son difíciles de dilucidar.
Objetivo del estudio:
- Para investigar el origen biosintético de las politeonamidas derivadas de esponjas marinas.
- Para identificar y caracterizar las enzimas responsables de las modificaciones post-traduccionales de estas toxinas.
- Comprender el mecanismo funcional de las politeonamidas como canales iónicos.
Principales métodos:
- Aislamiento de genes biosintéticos del metagenoma de la esponja marina.
- Análisis bioinformático para identificar enzimas candidatas involucradas en modificaciones post-traduccionales.
- Validación funcional de enzimas candidatas, incluida una enzima radical de S-adenosilmetionina.
Principales resultados:
- Los genes biosintéticos para las politeonamidas exhiben una arquitectura genética bacteriana.
- Se identificaron seis enzimas candidatas para 48 modificaciones postraslacionales, incluidas epimerizaciones y metilaciones extensas.
- Una enzima radical de S-adenosilmetionina fue validada para catalizar la epimerización unidireccional de múltiples aminoácidos.
Conclusiones:
- Las politeonamidas se sintetizan por ribosoma, lo que desafía el uso exclusivo de los aminoácidos l en los productos ribosómicos.
- Las complejas modificaciones post-traducionales, incluyendo la epimerización y la metilación, son cruciales para la función de la toxina.
- Estos hallazgos amplían las conocidas capacidades biosintéticas de los sistemas ribosómicos y ofrecen vías para la bioingeniería de péptidos.
Videos de Conceptos Relacionados
02:24Ribosome Profiling
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
01:56Riboswitches
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
02:53Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:44Termination of Translation
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...