scholarly journals The structure of the Pro-domain of mouse proNGF in contact with the NGF domain

2018 ◽  
Author(s):  
Robert Yan ◽  
Havva Yalinca ◽  
Francesca Paoletti ◽  
Francesco Gobbo ◽  
Laura Marchetti ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Functional Characterization ◽  
Functional Independence ◽  
Structural Features ◽  
Compact Structure ◽  
Hybrid Strategy ◽  
Growth And Survival ◽  
Functional Roles ◽  
Growth Cone Collapse ◽  
Protease Cleavage

AbstractNerve Growth Factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation, maintenance, growth and survival of target neurons. Expressed as a proNGF precursor, NGF is then matured by furin-mediated protease cleavage. Increasing evidence suggests that NGF and proNGF have distinct cellular partners which account for different functional roles. While the structure of mature NGF is available, little is known about the structure of the pro-domain within the context of proNGF because the dynamical and structural features of the protein have so far prevented its structure determination. We have exploited a new hybrid strategy based on nuclear magnetic resonance and modelling validated by small angle X-ray scattering to gain novel insights on the pro-domain, both in isolation and in the context of proNGF. We show that the isolated pro-domain is intrinsically unstructured but has a clear tertiary structure propensity and forms transient tertiary intramolecular contacts. It is also able to interact, albeit weakly, with mature NGF and has per se the ability to induce growth cone collapse, indicating functional independence. Based on paramagnetic relaxation enhancement data and advanced molecular modelling, we have then reconstructed the overall properties of the pro-domain in the context of proNGF and showed that it has a compact structure. Our data represent an important step towards the structural and functional characterization of the properties of proNGF and its pro-domain.

Insights into the Structural Features, Conformational Stability and Functional Activity of the Olneya tesota PF2 Lectin

2020 ◽  
Vol 27 ◽  
Author(s):  
Edgar Acedo-Espinoza ◽  
Irlanda Lagarda-Diaz ◽  
Rosina Cabrera ◽  
Ana M. Guzman-Partida ◽  
Amir Maldonado-Arce ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Proteolytic Enzymes ◽  
Conformational Stability ◽  
Structural Features ◽  
Beta Sheets ◽  
Hemagglutinating Activity ◽  
Effect Of Temperature ◽  
Hydrodynamic Diameter ◽  
Bioinformatic Tools ◽  
Structural Levels

Background: The O. tesota lectin PF2 is a tetrameric protein with subunits of 33 kDa that recognizes only complex carbohydrates, resistant to proteolytic enzymes and has insecticidal activity against Phaseolus beans pest. Objective: To explore PF2 lectin features at different protein structural levels and to evaluate the effect of temperature and pH on its functionality and conformational stability. Methods: PF2 lectin was purified by affinity chromatography. Its primary structure was resolved by mass spectrometry and analyzed by bioinformatic tools, including its tertiary structure homology modeling. The effect of temperature and pH on its conformational traits and stability was addressed by dynamic light scattering, circular dichroism, and intrinsic fluorescence. The hemagglutinating activity was evaluated using a suspension of peripheral blood erythrocytes. Results: The proposed PF2 folding comprises a high content of beta sheets. At pH 7 and 25 °C, the hydrodynamic diameter (Dh) was found to be 12.3 nm which corresponds to the oligomeric native state of PF2 lectin. Dh increased under the other evaluated pH and temperature conditions, suggesting protein aggregation. At basic pH, PF2 exhibited low conformational stability. The native PF2 (pH 7) retained its full hemagglutinating activity up to 45 °C and exhibited one transition state with a melting temperature of 76.8 °C. Conclusion: PF2 showed distinctive characteristics found in legume lectins. The pH influences the functionality and conformational stability of the protein. PF2 lectin displayed a relatively narrow thermostability to the loss of secondary structure and hemagglutinating activity.

scholarly journals Zoomqa: Residue-Level Single-Model QA Support Vector Machine Utilizing Sequential and 3D Structural Features

2021 ◽  
Author(s):  
Kyle Hippe ◽  
Cade Lilley ◽  
William Berkenpas ◽  
Kiyomi Kishaba ◽  
Renzhi Cao
Keyword(s):  
Protein Complex ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
State Of The Art ◽  
Chemical Properties ◽  
Structural Features ◽  
Residue Level ◽  
Support Vector ◽  
Single Model

ABSTRACTMotivationThe Estimation of Model Accuracy problem is a cornerstone problem in the field of Bioinformatics. When predictions are made for proteins of which we do not know the native structure, we run into an issue to tell how good a tertiary structure prediction is, especially the protein binding regions, which are useful for drug discovery. Currently, most methods only evaluate the overall quality of a protein decoy, and few can work on residue level and protein complex. Here we introduce ZoomQA, a novel, single-model method for assessing the accuracy of a tertiary protein structure / complex prediction at residue level. ZoomQA differs from others by considering the change in chemical and physical features of a fragment structure (a portion of a protein within a radius r of the target amino acid) as the radius of contact increases. Fourteen physical and chemical properties of amino acids are used to build a comprehensive representation of every residue within a protein and grades their placement within the protein as a whole. Moreover, ZoomQA can evaluate the quality of protein complex, which is unique.ResultsWe benchmark ZoomQA on CASP14, it outperforms other state of the art local QA methods and rivals state of the art QA methods in global prediction metrics. Our experiment shows the efficacy of these new features, and shows our method is able to match the performance of other state-of-the-art methods without the use of homology searching against database or PSSM matrix.Availabilityhttp://[email protected]

Molten globule state of human placental cystatin (HPC) at low pH conditions and the effects of trifluoroethanol (TFE) and methanol

2006 ◽  
Vol 84 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Fouzia Rashid ◽  
Sandeep Sharma ◽  
M A Baig ◽  
Bilqees Bano
Keyword(s):  
Conformational Changes ◽  
Tertiary Structure ◽  
Molten Globule ◽  
Structural Features ◽  
Cd Spectroscopy ◽  
Native State ◽  
Molten Globule State ◽  
Fluorescence Measurements ◽  
Helical Content ◽  
Human Placental Cystatin

Acid-induced conformational changes were studied in human placental cystatin (HPC) in terms of circular dichroism (CD) spectroscopy, the binding of hydrophobic dye 1-anilinonapthalene-8-sulphonic acid (ANS), and intrinsic fluorescence measurements. Our results show the formation of an acid-induced molten globule state at pH 2.0, with significant secondary and tertiary interactions that resemble the native state, exposed hydrophobic regions and the effects of trifluoroethanol (TFE) and methanol in conversion of the acid-denatured state of HPC to the alcohol-induced state, which is characterized by increased helical content, disrupted tertiary structure, and the absence of hydrophobic clusters. Alcohol-induced formation of α-helical structures at pH 2.0 is evident from the increase in the ellipticity values at 222 nm, with native-like secondary structural features at 40% TFE. The increase in helical content was observed up to 80% TFE concentration. The ability of TFE (40%) to refold acid-denatured HPC to native-state conformation is also supported by intrinsic and ANS fluorescence measurements.Key words: human placental cystatin, molten globule, acid-induced state, trifluoroethanol, methanol, CD spectroscopy, ANS fluorescence, pH, protein folding.

scholarly journals Investigation of the Relationship between the S1 Domain and Its Molecular Functions Derived from Studies of the Tertiary Structure

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3681 ◽  
Author(s):  
Evgenia I. Deryusheva ◽  
Andrey V. Machulin ◽  
Maxim A. Matyunin ◽  
Oxana V. Galzitskaya
Keyword(s):  
Protein Binding ◽  
Tertiary Structure ◽  
Relative Number ◽  
Structural Features ◽  
Statistical Tools ◽  
Binding Partners ◽  
Protein Functions ◽  
Domains Of Life ◽  
Molecular Functions ◽  
The Relationship

S1 domain, a structural variant of one of the “oldest” OB-folds (oligonucleotide/oligosaccharide-binding fold), is widespread in various proteins in three domains of life: Bacteria, Eukaryotes, and Archaea. In this study, it was shown that S1 domains of bacterial, eukaryotic, and archaeal proteins have a low percentage of identity, which indicates the uniqueness of the scaffold and is associated with protein functions. Assessment of the predisposition of tertiary flexibility of S1 domains using computational and statistical tools showed similar structural features and revealed functional flexible regions that are potentially involved in the interaction of natural binding partners. In addition, we analyzed the relative number and distribution of S1 domains in all domains of life and established specific features based on sequences and structures associated with molecular functions. The results correlate with the presence of repeats of the S1 domain in proteins containing the S1 domain in the range from one (bacterial and archaeal) to 15 (eukaryotic) and, apparently, are associated with the need for individual proteins to increase the affinity and specificity of protein binding to ligands.

scholarly journals Avian Pattern Recognition Receptor Sensing and Signaling

2020 ◽  
Vol 7 (1) ◽  
pp. 14 ◽  
Author(s):  
Sabari Nath Neerukonda ◽  
Upendra Katneni
Keyword(s):  
Pattern Recognition ◽  
Rational Design ◽  
Animal Species ◽  
Critical Role ◽  
Functional Characterization ◽  
Structural Features ◽  
Present Review ◽  
Vaccine Adjuvants ◽  
Microbial Defense ◽  
Recognition Receptor

Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti-microbial defense. Fundamental knowledge pertaining to the discovery of PRR functions and their ligands continue to advance the understanding of immune system and disease resistance, which led to the rational design and/or application of various PRR ligands as vaccine adjuvants. In addition, the conserved nature of many PRRs throughout the animal kingdom has enabled the utilization of the comparative genomics approach in PRR identification and the study of evolution, structural features, and functions in many animal species including avian. In the present review, we focused on PRR sensing and signaling functions in the avian species, domestic chicken, mallard, and domestic goose. In addition to summarizing recent advances in the understanding of avian PRR functions, the present review utilized a comparative biology approach to identify additional PRRs, whose functions have been well studied in mammalians but await functional characterization in avian.

Bacterial ß-Barrel Outer Membrane Proteins

2009 ◽  
pp. 182-207
Author(s):  
Pantelis G. Bagos ◽  
Stavros J. Hamodrakas
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Bacterial Cell ◽  
Outer Membrane Proteins ◽  
Structural Features ◽  
Structure And Function ◽  
Structural Motif ◽  
Functional Roles ◽  
Bacterial Outer Membrane ◽  
And Function

ß-barrel outer membrane proteins constitute the second and less well-studied class of transmembrane proteins. They are present exclusively in the outer membrane of Gram-negative bacteria and presumably in the outer membrane of mitochondria and chloroplasts. During the last few years, remarkable advances have been made towards an understanding of their functional and structural features. It is now wellknown that ß-barrels are performing a large variety of biologically important functions for the bacterial cell. Such functions include acting as specific or non-specific channels, receptors for various compounds, enzymes, translocation channels, structural proteins, and adhesion proteins. All these functional roles are of great importance for the survival of the bacterial cell under various environmental conditions or for the pathogenic properties expressed by these organisms. This chapter reviews the currently available literature regarding the structure and function of bacterial outer membrane proteins. We emphasize the functional diversity expressed by a common structural motif such as the ß-barrel, and we provide evidence from the current literature for dozens of newly discovered families of transmembrane ß-barrels.

scholarly journals Functional characterization of a non-AUUUA AU-rich element from the c-jun proto-oncogene mRNA: evidence for a novel class of AU-rich elements.

1996 ◽  
Vol 16 (4) ◽  
pp. 1490-1499 ◽  
Author(s):  
S S Peng ◽  
C Y Chen ◽  
A B Shyu
Keyword(s):  
Functional Characterization ◽  
Structural Features ◽  
Mrna Degradation ◽  
Beta Globin ◽  
Globin Mrna ◽  
Transcription Inhibitors ◽  
Tightly Coupled ◽  
Underlying Mechanisms ◽  
Necessary And Sufficient ◽  
Domain I

AU-rich RNA-destabilizing elements (AREs) found in the 3' untranslated regions of many labile mRNAs encoding proto-oncoproteins and cytokines generally contain (i) one or more copies of the AUUUA pentanucleotide and (ii) a high content of uridylate and sometimes also adenylate residues. Recently, we have identified a potent ARE from the 3' untranslated region of c-jun proto-oncogene mRNA that does not contain the AUUUA motif. In an attempt to further our understanding of the general principles underlying mechanisms by which AREs direct rapid and selective mRNA degradation, in this study we have characterized the functionally important structural features and properties of this non-AUUUA ARE. Like AUUUA-containing AREs, this non-AUUUA ARE directs rapid shortening of the poly(A) tail as a necessary first step for mRNA degradation. It can be further dissected into three structurally and functionally distinct regions, designated domains I, II, and III. None of three domains alone is able to significantly destabilize the stable beta-globin mRNA. The two unlinked domains, I and III, together are necessary and sufficient for specifying the full destabilizing function of this non-AUUUA ARE. Domain II appears functionally dispensable but can partially substitute for domain I. Domain swaps made between the c-jun non-AUUUA and the c-fos AUUUA-containing AREs reveal that the two AREs, while sharing no sequence homology, appear to contain sequence domains that are structurally distinct but functionally overlapping and exchangeable. These data support the idea that the ultimate destabilizing function of an individual ARE is determined by its own unique combination of structurally distinct and functionally interdependent domains. Our polysome profile studies show tha the destabilizing function of the c-jun non-AUUUA ARE does not require any active transit by ribosomes of the mRNA bearing it, further corroborating that the destabilizing function of AREs is not tightly coupled to ongoing translation by ribosomes. Moreover, unlike AUUUA-containing AREs, the c-jun ARE is insensitive to blockage of its effects by addition of transcription inhibitors. Thus, our data provide further evidence for the existence of a novel class of ARE with unique properties.

scholarly journals Expression and Functional Roles of Bradyrhizobium japonicum Genes Involved in the Utilization of Inorganic and Organic Sulfur Compounds in Free-Living and Symbiotic Conditions

2011 ◽  
Vol 24 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Masayuki Sugawara ◽  
Gopit R. Shah ◽  
Michael J. Sadowsky ◽  
Oleg Paliy ◽  
Justin Speck ◽  
...  
Keyword(s):  
Bradyrhizobium Japonicum ◽  
Gene Clusters ◽  
Sulfur Source ◽  
Organosulfur Compounds ◽  
In Planta ◽  
Growth And Survival ◽  
Functional Roles ◽  
Organic Sulfur Compounds ◽  
Sulfatase Activity ◽  
Bradyrhizobium Spp

Strains of Bradyrhizobium spp. form nitrogen-fixing symbioses with many legumes, including soybean. Although inorganic sulfur is preferred by bacteria in laboratory conditions, sulfur in agricultural soil is mainly present as sulfonates and sulfur esters. Here, we show that Bradyrhizobium japonicum and B. elkanii strains were able to utilize sulfate, cysteine, sulfonates, and sulfur-ester compounds as sole sulfur sources for growth. Expression and functional analysis revealed that two sets of gene clusters (bll6449 to bll6455 or bll7007 to bll7011) are important for utilization of sulfonates sulfur source. The bll6451 or bll7010 genes are also expressed in the symbiotic nodules. However, B. japonicum mutants defective in either of the sulfonate utilization operons were not affected for symbiosis with soybean, indicating the functional redundancy or availability of other sulfur sources in planta. In accordance, B. japonicum bacteroids possessed significant sulfatase activity. These results indicate that strains of Bradyrhizobium spp. likely use organosulfur compounds for growth and survival in soils, as well as for legume nodulation and nitrogen fixation.

scholarly journals Crystal structure of the PAS domain of the hEAG potassium channel

2016 ◽  
Vol 72 (8) ◽  
pp. 578-585 ◽  
Author(s):  
Xue Tang ◽  
Juan Shao ◽  
Xiaohong Qin
Keyword(s):  
Homo Sapiens ◽  
Cellular Responses ◽  
Structural Features ◽  
Pas Domain ◽  
Transmembrane Helices ◽  
Related Gene ◽  
Cellular Functions ◽  
Functional Roles ◽  
C Terminus ◽  
Β Sheet

KCNH voltage-gated potassium channels play critical roles in regulating cellular functions. The channel is composed of four subunits, each of which contains six transmembrane helices forming the central pore. The cytoplasmic parts of the subunits present a Per–Arnt–Sim (PAS) domain at the N-terminus and a cyclic nucleotide-binding homology domain at the C-terminus. PAS domains are conserved from prokaryotes to eukaryotes and are involved in sensing signals and cellular responses. To better understand the functional roles of PAS domains in KCNH channels, the structure of this domain from the humanether-à-go-gochannel (hEAG channel) was determined. By comparing it with the structures of theHomo sapiensEAG-related gene (hERG) channel and theDrosophilaEAG-like K+(dELK) channel and analyzing the structural features of the hEAG channel, it was identified that a hydrophobic patch on the β-sheet may mediate interaction between the PAS domain and other regions of the channel to regulate its functions.

scholarly journals TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae.

1991 ◽  
Vol 11 (8) ◽  
pp. 4266-4273 ◽  
Author(s):  
C H Ko ◽  
R F Gaber
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid Sequence Identity ◽  
Functional Independence ◽  
Structural Features ◽  
Low Ph ◽  
Sequence Identity ◽  
Hydrophilic Region ◽  
Membrane Spanning ◽  
Delta Cells ◽  
Membrane Spanning Domains

We describe the cloning and molecular analysis of TRK2, the gene likely to encode the low-affinity K+ transporter in Saccharomyces cerevisiae. TRK2 encodes a protein of 889 amino acids containing 12 putative membrane-spanning domains (M1 through M12), with a large hydrophilic region between M3 and M4. These structural features closely resemble those contained in TRK1, the high-affinity K+ transporter. TRK2 shares 55% amino acid sequence identity with TRK1. The putative membrane-spanning domains of TRK1 and TRK2 share the highest sequence conservation, while the large hydrophilic regions between M3 and M4 exhibit the greatest divergence. The different affinities of TRK1 trk2 delta cells and trk1 delta TRK2 cells for K+ underscore the functional independence of the high- and low-affinity transporters. TRK2 is nonessential in TRK1 or trk1 delta haploid cells. The viability of cells containing null mutations in both TRK1 and TRK2 reveals the existence of an additional, functionally independent potassium transporter(s). Cells deleted for both TRK1 and TRK2 are hypersensitive to low pH; they are severely limited in their ability to take up K+, particularly when faced with a large inward-facing H+ gradient, indicating that the K+ transporter(s) that remains in trk1 delta trk2 delta cells functions differently than those of the TRK class.

Sign in / Sign up

Export Citation Format

Share Document