scholarly journals The β-link motif in protein architecture

2021 ◽  
Vol 77 (8) ◽  
Author(s):  
David P. Leader ◽  
E. James Milner-White
Keyword(s):  
Serine Proteases ◽  
Polypeptide Chain ◽  
Cysteine Proteases ◽  
Type Ii ◽  
Terminal Portion ◽  
Structural Classification ◽  
Protein Motif ◽  
Protein Architecture ◽  
Α Helix ◽  
Β Sheet

The β-link is a composite protein motif consisting of a G1β β-bulge and a type II β-turn, and is generally found at the end of two adjacent strands of antiparallel β-sheet. The 1,2-positions of the β-bulge are also the 3,4-positions of the β-turn, with the result that the N-terminal portion of the polypeptide chain is orientated at right angles to the β-sheet. Here, it is reported that the β-link is frequently found in certain protein folds of the SCOPe structural classification at specific locations where it connects a β-sheet to another area of a protein. It is found at locations where it connects one β-sheet to another in the β-sandwich and related structures, and in small (four-, five- or six-stranded) β-barrels, where it connects two β-strands through the polypeptide chain that crosses an open end of the barrel. It is not found in larger (eight-stranded or more) β-barrels that are straightforward β-meanders. In some cases it initiates a connection between a single β-sheet and an α-helix. The β-link also provides a framework for catalysis in serine proteases, where the catalytic serine is part of a conserved β-link, and in cysteine proteases, including Mpro of human SARS-CoV-2, in which two residues of the active site are located in a conserved β-link.

scholarly journals Characterization of Hidden Chirality: Two-Fold Helicity in β-Strands

Symmetry ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 499 ◽  
Author(s):  
Toshiyuki Sasaki ◽  
Mikiji Miyata
Keyword(s):  
Hydrogen Bonds ◽  
Polypeptide Chain ◽  
Structural Motif ◽  
High Dimensional ◽  
Point Approximation ◽  
Β Sheets ◽  
Α Helix ◽  
Β Sheet

A β-strand is a component of a β-sheet and is an important structural motif in biomolecules. An α-helix has clear helicity, while chirality of a β-strand had been discussed on the basis of molecular twists generated by forming hydrogen bonds in parallel or non-parallel β-sheets. Herein we describe handedness determination of two-fold helicity in a zig-zag β-strand structure. Left- (M) and right-handedness (P) of the two-fold helicity was defined by application of two concepts: tilt-chirality and multi-point approximation. We call the two-fold helicity in a β-strand, whose handedness has been unrecognized and unclarified, as hidden chirality. Such hidden chirality enables us to clarify precise chiral characteristics of biopolymers. It is also noteworthy that characterization of chirality of high dimensional structures like a β-strand and α-helix, referred to as high dimensional chirality (HDC) in the present study, will contribute to elucidation of the possible origins of chirality and homochirality in nature because such HDC originates from not only asymmetric centers but also conformations in a polypeptide chain.

Scorpion toxin-potassium channel interaction law and its applications.

2020 ◽  
Vol 01 ◽  
Author(s):  
Zheng Zuo ◽  
Zongyun Chen ◽  
Zhijian Cao ◽  
Wenxin Li ◽  
Yingliang Wu
Keyword(s):  
Potassium Channel ◽  
Scorpion Toxin ◽  
Scorpion Toxins ◽  
Toxin Binding ◽  
Channel Interaction ◽  
Binding Interface ◽  
Α Helix ◽  
Interaction Law ◽  
Binding Interfaces ◽  
Β Sheet

: The scorpion toxins are the largest potassium channel-blocking peptide family. The understanding of toxin binding interfaces is usually restricted by two classical binding interfaces: one is the toxin α-helix motif, the other is the antiparallel β-sheet motif. In this review, such traditional knowledge was updated by another two different binding interfaces: one is BmKTX toxin using the turn motif between the α-helix and antiparallel β-sheet domains as the binding interface, the other is Ts toxin using turn motif between the β-sheet in the N-terminal and α-helix domains as the binding interface. Their interaction analysis indicated that the scarce negatively charged residues in the scorpion toxins played a critical role in orientating the toxin binding interface. In view of the toxin negatively charged amino acids as “binding interface regulator”, the law of scorpion toxin-potassium channel interaction was proposed, that is, the polymorphism of negatively charged residue distribution determines the diversity of toxin binding interfaces. Such law was used to develop scorpion toxin-potassium channel recognition control technique. According to this technique, three Kv1.3 channel-targeted peptides, using BmKTX as the template, were designed with the distinct binding interfaces from that of BmKTX through modulating the distribution of toxin negatively charged residues. In view of the potassium channel as the common targets of different animal toxins, the proposed law was also shown to helpfully orientate the binding interfaces of other animal toxins. Clearly, the toxin-potassium channel interaction law would strongly accelerate the research and development of different potassium channelblocking animal toxins in the future.

scholarly journals Phenotypic Analysis of Mice Lacking the Tmprss2-Encoded Protease

2006 ◽  
Vol 26 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Tom S. Kim ◽  
Cynthia Heinlein ◽  
Robert C. Hackman ◽  
Peter S. Nelson
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Biological Activities ◽  
Type Ii ◽  
Phenotypic Analysis ◽  
Normal Prostate ◽  
Prostate Hyperplasia ◽  
Transmembrane Serine Protease

ABSTRACT Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPRSS2 remain unknown. We generated Tmprss2 −/− mice by disrupting the serine protease domain through homologous recombination. Compared to wild-type littermates, Tmprss2 −/− mice developed normally, survived to adulthood with no differences in protein levels of prostatic secretions, and exhibited no discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine protease activity did not influence fertility, reduce survival, result in prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell regrowth following castration and androgen replacement. Lack of an observable phenotype in Tmprss2 −/− mice was not due to transcriptional compensation by closely related Tmprss2 homologs. We conclude that the lack of a discernible phenotype in Tmprss2 −/− mice suggests functional redundancy involving one or more of the type II transmembrane serine protease family members or other serine proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation.

scholarly journals Nanostructure of bioactive glass affects bone cell attachment via protein restructuring upon adsorption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ukrit Thamma ◽  
Tia J. Kowal ◽  
Matthias M. Falk ◽  
Himanshu Jain
Keyword(s):  
Bioactive Glass ◽  
Cell Response ◽  
Interfacial Layer ◽  
Cell Attachment ◽  
Bone Cell ◽  
Nano Structure ◽  
Rgd Sequence ◽  
Engineered Tissue ◽  
Α Helix ◽  
Β Sheet

AbstractThe nanostructure of engineered bioscaffolds has a profound impact on cell response, yet its understanding remains incomplete as cells interact with a highly complex interfacial layer rather than the material itself. For bioactive glass scaffolds, this layer comprises of silica gel, hydroxyapatite (HA)/carbonated hydroxyapatite (CHA), and absorbed proteins—all in varying micro/nano structure, composition, and concentration. Here, we examined the response of MC3T3-E1 pre-osteoblast cells to 30 mol% CaO–70 mol% SiO2 porous bioactive glass monoliths that differed only in nanopore size (6–44 nm) yet resulted in the formation of HA/CHA layers with significantly different microstructures. We report that cell response, as quantified by cell attachment and morphology, does not correlate with nanopore size, nor HA/CHO layer micro/nano morphology, or absorbed protein amount (bovine serum albumin, BSA), but with BSA’s secondary conformation as indicated by its β-sheet/α-helix ratio. Our results suggest that the β-sheet structure in BSA interacts electrostatically with the HA/CHA interfacial layer and activates the RGD sequence of absorbed adhesion proteins, such as fibronectin and vitronectin, thus significantly enhancing the attachment of cells. These findings provide new insight into the interaction of cells with the scaffolds’ interfacial layer, which is vital for the continued development of engineered tissue scaffolds.

scholarly journals Structural and Technological Approach to Reveal the Role of the Lipid Phase in the Formation of Soy Emulsion Gels with Chia Oil

Gels ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 48
Author(s):  
Ana M. Herrero ◽  
Claudia Ruiz-Capillas
Keyword(s):  
Raman Spectroscopy ◽  
Structural Properties ◽  
Structural Changes ◽  
Protein Secondary Structure ◽  
Lipid Phase ◽  
Α Helix ◽  
Β Sheet ◽  
Shed Light ◽  
Chia Oil

Considerable attention has been paid to emulsion gels (EGs) in recent years due to their interesting applications in food. The aim of this work is to shed light on the role played by chia oil in the technological and structural properties of EGs made from soy protein isolates (SPI) and alginate. Two systems were studied: oil-free SPI gels (SPI/G) and the corresponding SPI EGs (SPI/EG) that contain chia oil. The proximate composition, technological properties (syneresis, pH, color and texture) and structural properties using Raman spectroscopy were determined for SPI/G and SPI/EG. No noticeable (p > 0.05) syneresis was observed in either sample. The pH values were similar (p > 0.05) for SPI/G and SPI/EG, but their texture and color differed significantly depending on the presence of chia oil. SPI/EG featured significantly lower redness and more lightness and yellowness and exhibited greater puncture and gel strengths than SPI/G. Raman spectroscopy revealed significant changes in the protein secondary structure, i.e., higher (p < 0.05) α-helix and lower (p < 0.05) β-sheet, turn and unordered structures, after the incorporation of chia oil to form the corresponding SPI/EG. Apparently, there is a correlation between these structural changes and the textural modifications observed.

scholarly journals Assessment of Amyloid Forming Tendency of Peptide Sequences from Amyloid Beta and Tau Proteins Using Force-Field, Semi-Empirical, and Density Functional Theory Calculations

2021 ◽  
Vol 22 (6) ◽  
pp. 3244
Author(s):  
Charuvaka Muvva ◽  
Natarajan Arul Murugan ◽  
Venkatesan Subramanian
Keyword(s):  
Force Field ◽  
Density Functional ◽  
Amyloid Β ◽  
Density Functional Theory Calculations ◽  
Tau Proteins ◽  
Functional Theory ◽  
Energy Profiles ◽  
Α Helix ◽  
Semi Empirical ◽  
Β Sheet

A wide variety of neurodegenerative diseases are characterized by the accumulation of protein aggregates in intraneuronal or extraneuronal brain regions. In Alzheimer’s disease (AD), the extracellular aggregates originate from amyloid-β proteins, while the intracellular aggregates are formed from microtubule-binding tau proteins. The amyloid forming peptide sequences in the amyloid-β peptides and tau proteins are responsible for aggregate formation. Experimental studies have until the date reported many of such amyloid forming peptide sequences in different proteins, however, there is still limited molecular level understanding about their tendency to form aggregates. In this study, we employed umbrella sampling simulations and subsequent electronic structure theory calculations in order to estimate the energy profiles for interconversion of the helix to β-sheet like secondary structures of sequences from amyloid-β protein (KLVFFA) and tau protein (QVEVKSEKLD and VQIVYKPVD). The study also included a poly-alanine sequence as a reference system. The calculated force-field based free energy profiles predicted a flat minimum for monomers of sequences from amyloid and tau proteins corresponding to an α-helix like secondary structure. For the parallel and anti-parallel dimer of KLVFFA, double well potentials were obtained with the minima corresponding to α-helix and β-sheet like secondary structures. A similar double well-like potential has been found for dimeric forms for the sequences from tau fibril. Complementary semi-empirical and density functional theory calculations displayed similar trends, validating the force-field based free energy profiles obtained for these systems.

scholarly journals Reversed Proteolysis—Proteases as Peptide Ligases

Catalysts ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Peter Goettig
Keyword(s):  
Serine Proteases ◽  
Academic Research ◽  
Building Blocks ◽  
Peptide Bond ◽  
Cysteine Proteases ◽  
Small Peptides ◽  
Natural Peptide ◽  
Peptide Esters ◽  
Natural Amino Acids

Historically, ligase activity by proteases was theoretically derived due to their catalyst nature, and it was experimentally observed as early as around 1900. Initially, the digestive proteases, such as pepsin, chymotrypsin, and trypsin were employed to perform in vitro syntheses of small peptides. Protease-catalyzed ligation is more efficient than peptide bond hydrolysis in organic solvents, representing control of the thermodynamic equilibrium. Peptide esters readily form acyl intermediates with serine and cysteine proteases, followed by peptide bond synthesis at the N-terminus of another residue. This type of reaction is under kinetic control, favoring aminolysis over hydrolysis. Although only a few natural peptide ligases are known, such as ubiquitin ligases, sortases, and legumains, the principle of proteases as general catalysts could be adapted to engineer some proteases accordingly. In particular, the serine proteases subtilisin and trypsin were converted to efficient ligases, which are known as subtiligase and trypsiligase. Together with sortases and legumains, they turned out to be very useful in linking peptides and proteins with a great variety of molecules, including biomarkers, sugars or building blocks with non-natural amino acids. Thus, these engineered enzymes are a promising branch for academic research and for pharmaceutical progress.

Is folding of β-lactoglobulin non-hierarchic? intermediate with native-like β-sheet and non-native α-helix 1 1Edited by C. R. Matthews

2000 ◽  
Vol 296 (4) ◽  
pp. 1039-1051 ◽  
Author(s):  
Vincent Forge ◽  
Masaru Hoshino ◽  
Kazuo Kuwata ◽  
Munehito Arai ◽  
Kunihiro Kuwajima ◽  
...  
Keyword(s):  
Α Helix ◽  
Β Lactoglobulin ◽  
Β Sheet

scholarly journals Protein secondary structures (α-helix and β-sheet) at a cellular level and protein fractions in relation to rumen degradation behaviours of protein: a new approach

2005 ◽  
Vol 94 (5) ◽  
pp. 655-665 ◽  
Author(s):  
Peiqiang Yu
Keyword(s):  
Nutritive Value ◽  
Secondary Structures ◽  
Cellular Level ◽  
Heat Processing ◽  
Molecular Chemistry ◽  
New Approach ◽  
Ftir Microspectroscopy ◽  
Protein Secondary Structures ◽  
Α Helix ◽  
Β Sheet

Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the α-helix and β-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of β-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution (∼10 μm). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of α-helixes and β-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P<0·05) the percentage of α-helixes (from 47·1 % to 36·1 %: S-FTIR absorption intensity), increased the percentage of β-sheets (from 37·2 % to 49·8 %: S-FTIR absorption intensity) and reduced the α-helix to β-sheet ratio (from 0·3 to 0·7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate ‘pure’ protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours.

Sign in / Sign up

Export Citation Format

Share Document