Structural analysis of the dynamic ribosome-translocon complex DOI Creative Commons
Aaron J. O. Lewis,

Frank Zhong,

Robert J. Keenan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 22, 2023

Abstract The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-EM structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain conformation ribosomal uL22; translocon-associated (TRAP) complex adjust its position different stages biogenesis. Most unexpectedly, find large proportion complexes contains RAMP4 intercalated Sec61’s gate, widening central pore contributing hydrophilic interior. These structures lead mechanistic hypotheses for function highlight remarkably plastic machinery whose conformations composition dynamically diverse range substrates.

Язык: Английский

Structural analysis of the dynamic ribosome-translocon complex DOI Creative Commons
Aaron J. O. Lewis,

Frank Zhong,

Robert J. Keenan

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Июнь 18, 2024

The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-electron microscopy (cryo-EM) structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain conformation ribosomal uL22; translocon-associated (TRAP) complex adjust its position different stages biogenesis. Most unexpectedly, find large proportion complexes contains RAMP4 intercalated Sec61’s gate, widening central pore contributing hydrophilic interior. These structures lead mechanistic hypotheses for function highlight remarkably plastic machinery whose conformations composition dynamically diverse range substrates.

Язык: Английский

Процитировано

1
Multi-protein assemblies orchestrate co-translational enzymatic processing on the human ribosome DOI Open Access
Marius A. Klein, Klemens Wild, Irmgard Sinning

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Abstract Most nascent chains undergo rapid co-translational enzymatic processing as soon their N-terminus becomes accessible at the ribosomal polypeptide tunnel exit (PTE). In eukaryotes, N-terminal methionine excision (NME) by Methionine Aminopeptidases (MAP1 and MAP2), acetylation (NTA) N-Acetyl-Transferase A (NatA), is most common set of subsequent modifications carried out on ribosome. How these two processes are coordinated in quick succession context a rapidly translating ribosome has remained elusive. Here, we report that human NatA occupies non-intrusive ‘distal’ binding site which does not interfere with other associated factors (RAFs). this position, can partake dynamic assembly MAP1 through complex scaffolding function abundant Nascent Polypeptide Associated Complex (NAC). Alternatively, MAP2 co-occupy PTE preparation for successive NME NTA. contrast to MAP1, completely covers thus incompatible NAC recruitment. Both assemblies compile independent chain substrates. Together, our structures provide structural framework orchestration NTA protein biogenesis.

Язык: Английский

Процитировано

0
Reduction of ribosomal expansion segments in yeast species of the Magnusiomyces/Saprochaete clade DOI Creative Commons
Filip Brázdovič, Broňa Brejová, Barbara Siváková

и другие.

Genome Biology and Evolution, Год журнала: 2024, Номер unknown

Опубликована: Авг. 9, 2024

Ribosomes are ribonucleoprotein complexes highly conserved across all domains of life. The size differences ribosomal RNAs (rRNAs) can be mainly attributed to variable regions termed expansion segments (ESs) protruding out from the surface. ESs were found involved in a range processes including ribosome biogenesis and maturation, translation, co-translational protein modification. Here, we analyze rRNAs yeasts Magnusiomyces/Saprochaete clade belonging basal lineages subphylum Saccharomycotina. We find that these missing more than 400 nt 25S rRNA 150 18S when compared their canonical counterparts Saccharomyces cerevisiae. mostly map ESs, thus representing shift toward minimal structure. Despite structural changes rRNAs, did not identify dramatic alterations inventories. also show size-reduced limited species clade, indicating shortening happened independently several other

Язык: Английский

Процитировано

0
Reduction of ribosomal expansion segments in yeast species of theMagnusiomyces/Saprochaeteclade DOI Creative Commons
Filip Brázdovič, Broňa Brejová, Barbara Siváková

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 15, 2023

Abstract Ribosomes are ribonucleoprotein complexes highly conserved across all domains of life. The size differences ribosomal RNAs (rRNAs) can be mainly attributed to variable regions termed expansion segments (ESs) protruding out from the surface. ESs were found involved in a range processes including ribosome biogenesis and maturation, translation, co-translational protein modification. Here, we analyze rRNAs yeasts Magnusiomyces/Saprochaete clade belonging basal lineages subphylum Saccharomycotina. We find that these missing more than 400 nt 25S rRNA 150 18S when compared their canonical counterparts Saccharomyces cerevisiae . mostly map ESs, thus representing shift toward minimal structure. Despite structural changes rRNAs, did not identify dramatic alterations inventories. also show size-reduced limited species clade, indicating shortening happened independently several other Significance Expansion present translation. Although some them shown essential, functions evolutionary trajectories leading and/or reduction fully understood. have truncated segments, yet inventories ribosomes do radically differ possessing RNAs. loss occurred phylogenetic pointing dispensable nature. identified yeast open venue for further studies enigmatic elements eukaryotic ribosome.

Язык: Английский

Процитировано

0
Structural analysis of the dynamic ribosome-translocon complex DOI Creative Commons
Aaron J. O. Lewis,

Frank Zhong,

Robert J. Keenan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 22, 2023

Abstract The protein translocon at the endoplasmic reticulum comprises Sec61 translocation channel and numerous accessory factors that collectively facilitate biogenesis of secretory membrane proteins. Here, we leveraged recent advances in cryo-EM structure prediction to derive insights into several novel configurations ribosome-translocon complex. We show how a transmembrane domain (TMD) looped configuration passes through lateral gate during insertion; nascent chain can bind constrain conformation ribosomal uL22; translocon-associated (TRAP) complex adjust its position different stages biogenesis. Most unexpectedly, find large proportion complexes contains RAMP4 intercalated Sec61’s gate, widening central pore contributing hydrophilic interior. These structures lead mechanistic hypotheses for function highlight remarkably plastic machinery whose conformations composition dynamically diverse range substrates.

Язык: Английский

Процитировано

0