scholarly journals Cotranslational Folding of Proteins on the Ribosome

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 97 ◽  
Author(s):  
Marija Liutkute ◽  
Ekaterina Samatova ◽  
Marina V. Rodnina
Keyword(s):  
Protein Complexes ◽  
Single Domain ◽  
Oligomeric Proteins ◽  
Domain Structures ◽  
Cotranslational Folding ◽  
Exit Tunnel ◽  
Kinetic Traps ◽  
Early Compaction ◽  
Native Fold ◽  
Multiple Domain

Many proteins in the cell fold cotranslationally within the restricted space of the polypeptide exit tunnel or at the surface of the ribosome. A growing body of evidence suggests that the ribosome can alter the folding trajectory in many different ways. In this review, we summarize the recent examples of how translation affects folding of single-domain, multiple-domain and oligomeric proteins. The vectorial nature of translation, the spatial constraints of the exit tunnel, and the electrostatic properties of the ribosome-nascent peptide complex define the onset of early folding events. The ribosome can facilitate protein compaction, induce the formation of intermediates that are not observed in solution, or delay the onset of folding. Examples of single-domain proteins suggest that early compaction events can define the folding pathway for some types of domain structures. Folding of multi-domain proteins proceeds in a domain-wise fashion, with each domain having its role in stabilizing or destabilizing neighboring domains. Finally, the assembly of protein complexes can also begin cotranslationally. In all these cases, the ribosome helps the nascent protein to attain a native fold and avoid the kinetic traps of misfolding.

scholarly journals Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Taolan Zhao ◽  
Yan-Ming Chen ◽  
Yu Li ◽  
Jia Wang ◽  
Siyu Chen ◽  
...  
Keyword(s):  
Protein Quality ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
Translation Elongation ◽  
Cryo Electron Microscopy ◽  
Cotranslational Folding ◽  
A Cell ◽  
Exit Tunnel ◽  
Hidden Layer ◽  
A Site

Abstract Background The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRNA fragments protected by single ribosomes by ribo-seq. However, larger protected mRNA fragments have been observed, suggesting the existence of an alternative and previously hidden layer of regulation. Results In this study, we performed disome-seq to sequence mRNA fragments protected by two stacked ribosomes, a product of translational pauses during which the 5′-elongating ribosome collides with the 3′-paused one. We detected widespread ribosome collisions that are related to slow ribosome release when stop codons are at the A-site, slow peptide bond formation from proline, glycine, asparagine, and cysteine when they are at the P-site, and slow leaving of polylysine from the exit tunnel of ribosomes. The structure of disomes obtained by cryo-electron microscopy suggests a different conformation from the substrate of the ribosome-associated protein quality control pathway. Collisions occurred more frequently in the gap regions between α-helices, where a translational pause can prevent the folding interference from the downstream peptides. Paused or collided ribosomes are associated with specific chaperones, which can aid in the cotranslational folding of the nascent peptides. Conclusions Therefore, cells use regulated ribosome collisions to ensure protein homeostasis.

Substrate channels revealed in the trimericLactobacillus reuteribacterial microcompartment shell protein PduB

2012 ◽  
Vol 68 (12) ◽  
pp. 1642-1652 ◽  
Author(s):  
Allan Pang ◽  
Mingzhi Liang ◽  
Michael B. Prentice ◽  
Richard W. Pickersgill
Keyword(s):  
Tandem Repeats ◽  
Lactobacillus Reuteri ◽  
Protein Complexes ◽  
Protein Subunits ◽  
Shell Protein ◽  
Domain Structures ◽  
Bacterial Microcompartment ◽  
Major Shell ◽  
Carbon Molecules ◽  
Trimeric Structure

Lactobacillus reuterimetabolizes two similar three-carbon molecules, 1,2-propanediol and glycerol, within closed polyhedral subcellular bacterial organelles called bacterial microcompartments (metabolosomes). The outer shell of the propanediol-utilization (Pdu) metabolosome is composed of hundreds of mainly hexagonal protein complexes made from six types of protein subunits that share similar domain structures. The structure of the bacterial microcompartment protein PduB has a tandem structural repeat within the subunit and assembles into a trimer with pseudo-hexagonal symmetry. This trimeric structure forms sheets in the crystal lattice and is able to fit within a polymeric sheet of the major shell component PduA to assemble a facet of the polyhedron. There are three pores within the trimer and these are formed between the tandem repeats within the subunits. The structure shows that each of these pores contains three glycerol molecules that interact with conserved residues, strongly suggesting that these subunit pores channel glycerol substrate into the metabolosome. In addition to the observation of glycerol occupying the subunit channels, the presence of glycerol on the molecular threefold symmetry axis suggests a role in locking closed the central region.

Antiphase Domain Structures of CdTe on Sapphire Substrates

1987 ◽  
Vol 94 ◽  
Author(s):  
Kenji Maruyama ◽  
Mitsuo Yoshikawa ◽  
Hiroshi Takigawa
Keyword(s):  
Reaction Mechanism ◽  
Strong Correlation ◽  
Surface Reaction ◽  
Antiphase Domain ◽  
Cdte Layer ◽  
Single Domain ◽  
Rocking Curve ◽  
X Ray ◽  
Sapphire Substrates ◽  
Domain Structures

ABSTRACTAntiphase domain (APD) structures have been discovered in CdTe layers grown on (0001) sapphire substrates by MOCVD. To explain APD formation, an obstruction model based on a surface-reaction mechanism has been proposed. The proportion of one-phase domains to the total area varies with the [DETe]/[DMCd] ratio (VI/II ratio). A single-domain CdTe layer can be obtained at a VI/II ratio of 5. The APD structure shows a strong correlation with the crystallinity measured by X-ray. For a single-domain CdTe epilayer, theFWHM of the X-ray rocking curve shows 114 arc seconds and the EPD is 6×10 cm−2

scholarly journals Gradual Compaction of the Nascent Peptide During Cotranslational Folding on the Ribosome

2020 ◽  
Author(s):  
Marija Liutkute ◽  
Manisankar Maiti ◽  
Ekaterina Samatova ◽  
Jörg Enderlein ◽  
Marina V. Rodnina
Keyword(s):  
Profile Analysis ◽  
Dynamic Properties ◽  
Correlation Spectroscopy ◽  
Fluorescence Correlation ◽  
Cotranslational Folding ◽  
Nascent Peptide ◽  
Nascent Chain ◽  
Force Profile ◽  
Exit Tunnel ◽  
Domain Stabilization

ABSTRACTNascent polypeptides begin to fold in the constrained space of the ribosomal peptide exit tunnel. Here we use force profile analysis (FPA) and photo-induced energy-transfer fluorescence correlation spectroscopy (PET-FCS) to show how a small α-helical domain, the N-terminal domain of HemK, folds cotranslationally. Compaction starts vectorially as soon as the first α-helical segments are synthesized. As nascent chain grows, emerging helical segments dock onto each other and continue to rearrange at the vicinity of the ribosome. Inside or in the proximity of the ribosome, the nascent peptide undergoes structural fluctuations on the μs time scale. The fluctuations slow down as the domain moves away from the ribosome. Folding mutations have little effect on folding within the exit tunnel, but abolish the final domain stabilization. The results show the power of FPA and PET-FCS in solving the trajectory of cotranslational protein folding and in characterizing the dynamic properties of folding intermediates.

scholarly journals Synthesis and ESR Study of Transition from Ferromagnetism to Superparamagnetism in La0.8Sr0.2MnO3 Nanomanganite

2020 ◽  
Author(s):  
Mondher Yahya ◽  
Faouzi Hosni ◽  
Ahmed Hichem Hamzaoui
Keyword(s):  
Crystallite Size ◽  
Magnetic State ◽  
Resonance Field ◽  
Magnetic Domain ◽  
Single Domain ◽  
State Transitions ◽  
G Factor ◽  
Domain Structures ◽  
Crystallite Sizes ◽  
Superparamagnetic State

Electron spin resonance (ESR) spectroscopy was used to determine the magnetic state transitions of nanocrystalline La0.8Sr0.2MnO3 at room temperature, as a function of crystallite size. Ferromagnetic nanoparticles having an average crystallite size ranging from 9 to 57 nm are prepared by adopting the autocombustion method with two-step synthesis process. Significant changes of the ESR spectra parameters, such as the line shape, resonance field (Hr), g-factor, linewidth (∆Hpp), and the low-field microwave absorption (LFMA) signal, are indicative of the change in magnetic domain structures from superparamagnetism to single-domain and multi-domain ferromagnetism by increase in the crystallite size. Samples with crystallite sizes less than 24.5 nm are in a superparamagnetic state. Between 24.5 and 32 nm, they are formed by a single-domain ferromagnetic. The multi-domain state arises for higher sizes. In superparamagnetic region, the value of g-factor is practically constant suggesting that the magnetic core size is invariant with decreasing crystallite size. This contradictory observation with the core-shell model was explained by the phenomenon of phase separation that leads to the formation of a new magnetic state that we called multicore superparamagnetic state.

scholarly journals The architectural design of networks of protein domain architectures

2013 ◽  
Vol 9 (4) ◽  
pp. 20130268 ◽  
Author(s):  
Chia-Hsin Hsu ◽  
Chien-Kuo Chen ◽  
Ming-Jing Hwang
Keyword(s):  
Architectural Design ◽  
Molecular Form ◽  
Protein Domains ◽  
Single Domain ◽  
Protein Domain ◽  
Protein Architecture ◽  
Different Types ◽  
Protein Functions ◽  
Shed Light ◽  
Multiple Domain

Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

scholarly journals Cotranslational folding allows misfolding-prone proteins to circumvent deep kinetic traps

2020 ◽  
Vol 117 (3) ◽  
pp. 1485-1495 ◽  
Author(s):  
Amir Bitran ◽  
William M. Jacobs ◽  
Xiadi Zhai ◽  
Eugene Shakhnovich
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Folding Kinetics ◽  
Rare Codons ◽  
Cotranslational Folding ◽  
Nascent Chain ◽  
Kinetic Traps ◽  
Optimal Window

Many large proteins suffer from slow or inefficient folding in vitro. It has long been known that this problem can be alleviated in vivo if proteins start folding cotranslationally. However, the molecular mechanisms underlying this improvement have not been well established. To address this question, we use an all-atom simulation-based algorithm to compute the folding properties of various large protein domains as a function of nascent chain length. We find that for certain proteins, there exists a narrow window of lengths that confers both thermodynamic stability and fast folding kinetics. Beyond these lengths, folding is drastically slowed by nonnative interactions involving C-terminal residues. Thus, cotranslational folding is predicted to be beneficial because it allows proteins to take advantage of this optimal window of lengths and thus avoid kinetic traps. Interestingly, many of these proteins’ sequences contain conserved rare codons that may slow down synthesis at this optimal window, suggesting that synthesis rates may be evolutionarily tuned to optimize folding. Using kinetic modeling, we show that under certain conditions, such a slowdown indeed improves cotranslational folding efficiency by giving these nascent chains more time to fold. In contrast, other proteins are predicted not to benefit from cotranslational folding due to a lack of significant nonnative interactions, and indeed these proteins’ sequences lack conserved C-terminal rare codons. Together, these results shed light on the factors that promote proper protein folding in the cell and how biomolecular self-assembly may be optimized evolutionarily.

scholarly journals Does Empirically Derived Classification of Individuals with Subjective Cognitive Complaints Predict Dementia?

2019 ◽  
Vol 9 (11) ◽  
pp. 314 ◽  
Author(s):  
Picón ◽  
Juncos-Rabadán ◽  
Lojo-Seoane ◽  
Campos-Magdaleno ◽  
Mallo ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Cognitive Decline ◽  
Hierarchical Cluster ◽  
Single Domain ◽  
Subjective Cognitive Decline ◽  
Cognitive Complaints ◽  
Clinical Criteria ◽  
Amnestic Mci ◽  
Multiple Domain ◽  
Subjective Cognitive Complaints

(1) Background: Early identification of mild cognitive impairment (MCI) in people reporting subjective cognitive complaints (SCC) and the study of progression of cognitive decline are important issues in dementia research. This paper examines whether empirically derived procedures predict progression from MCI to dementia. (2) Methods: At baseline, 192 participants with SCC were diagnosed according to clinical criteria as cognitively unimpaired (70), single-domain amnestic MCI (65), multiple-domain amnestic MCI (33) and multiple-domain non-amnestic MCI (24). A two-stage hierarchical cluster analysis was performed for empirical classification. Categorical regression analysis was then used to assess the predictive value of the clusters obtained. Participants were re-assessed after 36 months. (3) Results: Participants were grouped into four empirically derived clusters: Cluster 1, similar to multiple-domain amnestic MCI; Cluster 2, characterized by subjective cognitive decline (SCD) but with low scores in language and working memory; Cluster 3, with specific deterioration in episodic memory, similar to single-domain amnestic MCI; and Cluster 4, with SCD but with scores above the mean in all domains. The majority of participants who progressed to dementia were included in Cluster 1. (4) Conclusions: Cluster analysis differentiated between MCI and SCD in a sample of people with SCC and empirical criteria were more closely associated with progression to dementia than standard criteria.

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