scholarly journals The N terminus of the molecular chaperonin GroEL is a crucial structural element for its assembly

1993 ◽  
Vol 268 (14) ◽  
pp. 9957-9959
Author(s):  
A. Horovitz ◽  
E.S. Bochkareva ◽  
A.S. Girshovich
2019 ◽  
Author(s):  
H. Mesa-Galloso ◽  
P.A. Valiente ◽  
R.F. Epand ◽  
M.E. Lanio ◽  
R.M. Epand ◽  
...  

AbstractSticholysins are pore-forming toxins of biomedical interest and represent a prototype of proteins acting through the formation of protein-lipid or toroidal pores. Peptides spanning the N-terminus of sticholysins can mimic their permeabilizing activity and together with the full-length toxins have been used as a tool to understand the mechanism of pore formation in membranes. However, the lytic mechanism of these peptides and the lipid shape modulating their activity are not completely clear. In this paper, we combine molecular dynamics (MD) simulations and experimental biophysical tools to dissect different aspects of the pore-forming mechanism of StII1-30, a peptide derived from the N-terminus of sticholysin II. With this combined approach, membrane curvature induction and flip-flop movement of the lipids were identified as two important membrane remodeling steps mediated by StII1-30-pore forming activity. Pore-formation by this peptide was enhanced by the presence of the negatively-curved lipid phosphatidylethanolamine (PE) in membranes. This lipid emerged not only as a facilitator of membrane interactions but also as a structural element of the StII1-30-pore that is recruited to the pore ring upon its assembly. Collectively, these new findings support a toroidal model for the architecture of the pore formed by this peptide and provide new molecular insight into the role of PE as a membrane component that easily accommodates into the ring of toroidal pores aiding in its stabilization. This study contributes to a better understanding of the molecular mechanism underlying the permeabilizing activity of StII1-30 and peptides or proteins acting via a toroidal pore mechanism and offers an informative framework for the optimization of the biomedical application of this and similar molecules.State of significanceWe provide evidence about the ability of StII1-30 to form toroidal pores. Due to pore assembly, StII1-30-pore induces membrane curvature and facilitates flip-flop movement of the lipids. The negatively-curved lipid PE relocates from the membrane into the pore ring, being also a structural element of the pore StII1-30 forms. This peptide emerged as a new tool, together with the full-length toxin, to understand the mechanism of toroidal pore formation in membranes. This study provides new molecular insight into the role of curved lipids as co-factors of toroidal pores, which could aid in its stabilization by easily accommodating into the ring. This framework could underpin strategies for the rational use of peptides or proteins acting via toroidal pores.


Author(s):  
James F. Hainfeld ◽  
Frederic R. Furuya ◽  
Kyra Carbone ◽  
Martha Simon ◽  
Beth Lin ◽  
...  

A recently developed 1.4 nm gold cluster has been found to be useful in labeling macromolecular sites to 1-3 nm resolution. The gold compound is organically derivatized to contain a monofunctional arm for covalent linking to biomolecules. This may be used to mark a specific site on a structure, or to first label a component and then reassemble a multicomponent macromolecular complex. Two examples are given here: the chaperonin groEL and ribosomes.Chaperonins are essential oligomeric complexes that mediate nascent polypeptide chain folding to produce active proteins. The E. coli chaperonin, groEL, has two stacked rings with a central hole ∽6 nm in diameter. The protein dihydrofolate reductase (DHFR) is a small protein that has been used in chain folding experiments, and serves as a model substrate for groEL. By labeling the DHFR with gold, its position with respect to the groEL complex can be followed. In particular, it was sought to determine if DHFR refolds on the external surface of the groEL complex, or whether it interacts in the central cavity.


2020 ◽  
Vol 90 (5-6) ◽  
pp. 411-416 ◽  
Author(s):  
Carina Kolot ◽  
Ana Rodriguez-Mateos ◽  
Rodrigo Feliciano ◽  
Katharina Bottermann ◽  
Wilhelm Stahl

Abstract. Chalcones are a type of flavonoids characterized by an α-β unsaturated structural element which may react with thiol groups to activate pathways such as the Nrf2-Keap-1 system. Naringenin chalcone is abundant in the diet but little is known about its bioavailability. In this work, the bioavailability of naringenin chalcone from tomatoes was investigated in a group of healthy men (n=10). After ingestion of 600 grams of tomatoes providing a single dose of 17.3 mg naringenin chalcone, 0.2 mg of naringenin, and 195 mg naringin plasma levels of free and conjugated naringenin and naringenin chalcone (glucuronide and sulfate) were analyzed by UHPLC-QTOF-MS at 0.5, 1, 3, and 6 h post-consumption. Plasma levels of conjugated naringenin increased to about 12 nmol/L with a maximum at about 3 h. Concentrations of free naringenin hardly elevated above baseline. Plasma levels of free and conjugated naringenin chalcone significantly increased. A maximum of the conjugated chalcone was reached at about 3 h after ingestion with an average concentration of about 0.5 nmol/L. No free chalcone was detectable at baseline but low amounts of the unconjugated compound could be detected with an average maximum of 0.8 nmol/L at about 1 h after ingestion. The data demonstrate that naringenin chalcone is bioavailable in humans from cherry tomatoes as a dietary source. However, availability is poor and intramolecular cyclisation as well as extended metabolism likely contribute to the inactivation of the reactive alpha-beta unsaturated reactive center as well as the excretion of the biologically active molecule, respectively.


1998 ◽  
Vol 80 (08) ◽  
pp. 310-315 ◽  
Author(s):  
Marie-Christine Bouton ◽  
Christophe Thurieau ◽  
Marie-Claude Guillin ◽  
Martine Jandrot-Perrus

SummaryThe interaction between GPIb and thrombin promotes platelet activation elicited via the hydrolysis of the thrombin receptor and involves structures located on the segment 238-290 within the N-terminal domain of GPIbα and the positively charged exosite 1 on thrombin. We have investigated the ability of peptides derived from the 269-287 sequence of GPIbα to interact with thrombin. Three peptides were synthesized, including Ibα 269-287 and two scrambled peptides R1 and R2 which are comparable to Ibα 269-287 with regards to their content and distribution of anionic residues. However, R2 differs from both Ibα 269-287 and R1 by the shifting of one proline from a central position to the N-terminus. By chemical cross-linking, we observed the formation of a complex between 125I-Ibα 269-287 and α-thrombin that was inhibited by hirudin, the C-terminal peptide of hirudin, sodium pyrophosphate but not by heparin. The complex did not form when γ-thrombin was substituted for α-thrombin. Ibα 269-287 produced only slight changes in thrombin amidolytic activity and inhibited thrombin binding to fibrin. R1 and R2 also formed complexes with α-thrombin, modified slightly its catalytic activity and inhibited its binding to fibrin. Peptides Ibα 269-287 and R1 inhibited platelet aggregation and secretion induced by low thrombin concentrations whereas R2 was without effect. Our results indicate that Ibα 269-287 interacts with thrombin exosite 1 via mainly electrostatic interactions, which explains why the scrambled peptides also interact with exosite 1. Nevertheless, the lack of effect of R2 on thrombin-induced platelet activation suggests that proline 280 is important for thrombin interaction with GPIb.


BioResources ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. 7079-7099
Author(s):  
Jianying Chen ◽  
Guojing He ◽  
Xiaodong (Alice) Wang ◽  
Jiejun Wang ◽  
Jin Yi ◽  
...  

Timber-concrete composite beams are a new type of structural element that is environmentally friendly. The structural efficiency of this kind of beam highly depends on the stiffness of the interlayer connection. The structural efficiency of the composite was evaluated by experimental and theoretical investigations performed on the relative horizontal slip and vertical uplift along the interlayer between composite’s timber and concrete slab. Differential equations were established based on a theoretical analysis of combination effects of interlayer slip and vertical uplift, by using deformation theory of elastics. Subsequently, the differential equations were solved and the magnitude of uplift force at the interlayer was obtained. It was concluded that the theoretical calculations were in good agreement with the results of experimentation.


Metahumaniora ◽  
2017 ◽  
Vol 7 (3) ◽  
pp. 293
Author(s):  
Tania Intan

AbstrakSecara alamiah, manusia membutuhkan sarana untuk mengisi waktu luangnyasetelah bekerja keras. Satu media yang murah, mudah dijangkau, dan digemari oleh semuakalangan di seluruh dunia adalah cerita bergambar atau komik yang merupakan bagiandari budaya populer. Pada umumnya, karya paraliteratur-visual ini memang bersifat fiktifdan hanya merupakan peniruan dari kenyataan yang digambarkan secara berlebihan(grotesque). Namun demikian, di dalam komik, sering ditemukan nilai-nilai kehidupanyang bersifat universal dan abadi sehingga dianggap layak sebagai bahan kajian budaya.Naruto, salah satu manga Jepang, dan Astérix, bande dessinée dari Prancis, akan ditelitisebagai representasi dunia Timur dan Barat. Latar sebagai unsur struktural dalam karyakaryafiksi ini ternyata juga menunjukkan kesamaan mendasar, yaitu keberadaan desasebagai tempat hidup para tokohnya. Dalam tulisan ini, akan dibahas pemaknaan lainterhadap lingkungan rural tersebut, yang memiliki andil dalam pembentukan karakterpara tokoh dari kedua komik. Metode kajian komparasi budaya akan digunakan denganpenerapan teori-teori yang relevan. Penelitian singkat ini bertujuan untuk melengkapistudi mengenai komik yang belum banyak dilakukan di Indonesia.Kata kunci: Desa, komik, Naruto, Astérix, Komparasi BudayaAbstractNaturally, humans need a way to fill their spare time after working hard. Acheap, accessible and popular medium by all circles around the world is a picture or comicstory, which is part of popular culture. McCloud (1993:7) defines comics as drawings andembossed symbols in a particular order, aimed at providing information or achievingaesthetic responses from the reader. In general, this visual-paraliterature work isindeed fictitious and merely an imitation of grotesque reality. However, in the comics, itis often found that values of life that are universal and eternal so comics are consideredappropriate as a material of cultural studies. Naruto, one of the Japanese manga, andAstérix, the bande dessinée of France, are examined as a representation of the East andWest. The background as a structural element in these works of fiction also shows the basicsimilarity of the existence of the village as the place of life of the characters. According toKartohadikoesoemo (1984:16), the village is a legal entity, in which a ruling society livesits own government. In this paper, other meanings of the rural environment, which hascontributed in the character formation of the characters from both comics are discussed.The method of cultural comparative is used with the application of relevant theories. Thisbrief study aims to complete the study of comics which is still very limited in Indonesia.Keywords: Village, Comic, Naruto, Astérix, Cultural Comparison


2016 ◽  
Vol 4 (Suppl. 3) ◽  
pp. A4.17
Author(s):  
Fatma Aslı Erdem
Keyword(s):  

2020 ◽  
pp. 60-63
Author(s):  
Elena Senina

The author analyzes the category of viability as a structural element of social adaptation of patients who underwent revisional hip replacement. Considering the process of postoperative rehabilitation, the author focuses on viability as an individual characteristic of patients, which determines the effectiveness of physical recovery and social adaptation after hip replacement. The article observes the results of an empirical study conducted on the basis of Saratov Research Institute of Traumatology and Orthopedics of Minzdrav of Russia, aimed at studying the criteria of viability and social viability of adaptation and social adaptation.


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