scholarly journals Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ

2021 ◽  
Vol 22 (19) ◽  
pp. 10408
Author(s):  
Alexander Eckersley ◽  
Matiss Ozols ◽  
Peikai Chen ◽  
Vivian Tam ◽  
Judith A. Hoyland ◽  
...  
Keyword(s):  
Structural Damage ◽  
Biomarker Discovery ◽  
Protein Structures ◽  
Human Organ ◽  
Protease Cleavage ◽  
Location Fingerprinting ◽  
Analysis Technique ◽  
Structural Differences ◽  
Tissue Region ◽  
Collagen Ii

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus) identified 268 proteins with age-associated structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and -resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I α2, collagen II α1 and collagen V α1, were located within their triple-helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance. Several proteins (collagen V α1, collagen II α1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young samples, suggesting that some ageing mechanisms may act locally within tissues. This study not only reveals possible age-associated differences in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF as a proteomic tool to aid in biomarker discovery.

scholarly journals Peptide Location Fingerprinting Reveals Tissue Region-specific Differences in Protein Structures in an Ageing Human Organ

2021 ◽  
Author(s):  
Alexander Eckersley ◽  
Matiss Ozols ◽  
Peikai Chen ◽  
Vivian Tam ◽  
Judith A Hoyland ◽  
...  
Keyword(s):  
Structural Damage ◽  
Protein Structures ◽  
Protein Biomarkers ◽  
Tissue Remodelling ◽  
Human Organ ◽  
Location Fingerprinting ◽  
Age Related ◽  
Analysis Technique ◽  
Structural Differences ◽  
Tissue Region

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus), identified 268 proteins with age-related structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I, II and V α-chains (COL1A2, COL2A1, COL5A1), were located within their triple helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance in ageing. Several proteins (COL5A1, COL2A1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young, suggesting that some ageing mechanisms may act locally within tissues. This study not only provides evidence of age-related changes in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF to identify potential protein biomarkers of localised tissue remodelling.

scholarly journals Peptide location fingerprinting reveals modification-associated biomarkers of ageing in human tissue proteomes

2020 ◽  
Author(s):  
Matiss Ozols ◽  
Alexander Eckersley ◽  
Kieran T Mellody ◽  
Venkatesh Mallikarjun ◽  
Stacey Warwood ◽  
...  
Keyword(s):  
Structural Modification ◽  
Protein Structures ◽  
Cytoskeletal Proteins ◽  
Structural Modifications ◽  
Location Fingerprinting ◽  
Age Related ◽  
Analysis Technique ◽  
Key Factor ◽  
Aged Skin ◽  
Novel Biomarkers

AbstractAlthough dysfunctional protein homeostasis (proteostasis) is a key factor in many age-related diseases, the untargeted identification of structural modifications in proteins remains challenging. Peptide location fingerprinting is a proteomic analysis technique capable of identifying structural modification-associated differences in mass spectrometry (MS) datasets of complex biological samples. A new webtool (Manchester Peptide Location Fingerprinter), applied to photoaged and intrinsically aged skin proteomes, can relatively quantify peptides (spectral counting) and map statistically significant differences to regions within protein structures. New photoageing biomarkers were identified in multiple proteins including matrix components (collagens and proteoglycans), oxidation and protease modulators (peroxiredoxins and SERPINs) and cytoskeletal proteins (keratins). Crucially, for many extracellular biomarkers, structural modification-associated differences were not correlated with relative abundance (by ion intensity). By applying peptide location fingerprinting to published MS datasets, (identifying biomarkers including collagen V and versican in ageing tendon) we demonstrate the potential of the MPLF webtool to discover novel biomarkers.

Robustness and Efficiency of an Optimization-Based Damage Detection Technique

2014 ◽  
Author(s):  
Chulho Yang ◽  
Douglas E. Adams
Keyword(s):  
Structural Dynamics ◽  
Structural Damage ◽  
Damage Identification ◽  
Response Functions ◽  
Identification Process ◽  
Sensitivity Functions ◽  
Design Variables ◽  
Analysis Technique ◽  
Measured Frequency Response ◽  
The Difference

A structural damage identification method based on sensitivity functions and optimization algorithms is discussed in this paper. The suggested sensitivity analysis technique can be effectively used for the damage identification process because it requires only measured frequency response functions to calculate the sensitivity of system responses to each component parameter. The optimization algorithm finds the best combination of changes in design variables to minimize the object function that is defined as the difference between the measured and calculated FRFs for the damaged structure. Various parameters and factors in the optimization process and structural dynamics are studied in this work to enhance the efficiency and robustness of the damage identification process. This study shows that the proposed technique can improve the accuracy of damage identification.

scholarly journals FATCAT 2.0: towards a better understanding of the structural diversity of proteins

2020 ◽  
Vol 48 (W1) ◽  
pp. W60-W64
Author(s):  
Zhanwen Li ◽  
Lukasz Jaroszewski ◽  
Mallika Iyer ◽  
Mayya Sedova ◽  
Adam Godzik
Keyword(s):  
Protein Structures ◽  
Structural Diversity ◽  
Structure Alignment ◽  
Protein Structure Alignment ◽  
Alignment Algorithm ◽  
Graphical Interface ◽  
Structural Differences ◽  
Functional Forms ◽  
Crystallization Conditions ◽  
Flexible Protein

Abstract FATCAT 2.0 server (http://fatcat.godziklab.org/), provides access to a flexible protein structure alignment algorithm developed in our group. In such an alignment, rotations and translations between elements in the structure are allowed to minimize the overall root mean square deviation (RMSD) between the compared structures. This allows to effectively compare protein structures even if they underwent structural rearrangements in different functional forms, different crystallization conditions or as a result of mutations. The major update for the server introduces a new graphical interface, much faster database searches and several new options for visualization of the structural differences between proteins

scholarly journals A comparative analysis of parechovirus protein structures with other picornaviruses

Open Biology ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 210008
Author(s):  
Aušra Domanska ◽  
Sergey Guryanov ◽  
Sarah J. Butcher
Keyword(s):  
Comparative Analysis ◽  
Structure Prediction ◽  
Protein Structures ◽  
Respiratory Illness ◽  
Polyprotein Processing ◽  
Original Analysis ◽  
Animal Pathogens ◽  
The Family ◽  
Structural Differences ◽  
Icosahedral Viruses

Parechoviruses belong to the genus Parechovirus within the family Picornaviridae and are non-enveloped icosahedral viruses with a single-stranded RNA genome. Parechoviruses include human and animal pathogens classified into six species. Those that infect humans belong to the Parechovirus A species and can cause infections ranging from mild gastrointestinal or respiratory illness to severe neonatal sepsis. There are no approved antivirals available to treat parechovirus (nor any other picornavirus) infections. In this parechovirus review, we focus on the cleaved protein products resulting from the polyprotein processing after translation comparing and contrasting their known or predicted structures and functions to those of other picornaviruses. The review also includes our original analysis from sequence and structure prediction. This review highlights significant structural differences between parechoviral and other picornaviral proteins, suggesting that parechovirus drug development should specifically be directed to parechoviral targets.

scholarly journals Nonlinear Dynamic Behavior of the Human Knee Joint—Part II: Time-Domain Analyses: Effects of Structural Damage in Postmortem Experiments

1991 ◽  
Vol 113 (4) ◽  
pp. 392-396 ◽  
Author(s):  
Dortmans ◽  
H. Jans ◽  
A. Sauren ◽  
A. Huson
Keyword(s):  
Knee Joint ◽  
Dynamic Behavior ◽  
Time Domain ◽  
Nonlinear Dynamic ◽  
Structural Damage ◽  
Time Domain Analysis ◽  
Human Knee ◽  
Human Knee Joint ◽  
Analysis Technique ◽  
Stiffness And Damping

A description is given of the results obtained for step excitation for two human knee joint specimens using a time-domain analysis technique. As was expected from the results of a previous study, the magnitude of the dynamic load applied has a marked influence upon the stiffness and damping values for the two observed vibration modes. Deliberate damaging of selected joint elements also yields a well observable change in the dynamic behavior of the joint although these changes are difficult to interpret. Here the use of a nonlinear dynamic numerical model of the knee joint seems indispensable. An important observation is, however, that the experimental method discussed here enables to quantify the behavior of the joint and therefore may provide a valuable tool for validation of such a model.

scholarly journals A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2

2020 ◽  
Author(s):  
Konstantina Karathanou ◽  
Michalis Lazaratos ◽  
Éva Bertalan ◽  
Malte Siemers ◽  
Krzysztof Buzar ◽  
...  
Keyword(s):  
Host Cell ◽  
Communication Networks ◽  
Protein Structures ◽  
Protein S ◽  
Spike Protein ◽  
Structural Elements ◽  
Angiotensin Converting Enzyme 2 ◽  
Protease Cleavage ◽  
Carboxylate Groups ◽  
Conformational Plasticity

AbstractCorona virus spike protein S is a large homo-trimeric protein embedded in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, has a relatively large H-bond cluster at the receptor binding domain, and a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.

Statistics-Based Noise Analysis for Vibration-Based Damage Identification

2006 ◽  
Author(s):  
L. Yu ◽  
T. Yin ◽  
H. P. Zhu
Keyword(s):  
Damage Detection ◽  
Structural Damage ◽  
Damage Identification ◽  
Perturbation Technique ◽  
Random Perturbation ◽  
Noise Analysis ◽  
Detection Methods ◽  
Mode Shapes ◽  
Composite Function ◽  
Analysis Technique

As the vibration-based structural damage detection methods are easily affected by the environmental noise, a novel noise analysis method is proposed based on the statistics in this paper together with the Monte Carlo technique for assessing the influence of experimental noise of modal data on sensitivity-based damage detection methods. Different from the commonly used random perturbation technique, the proposed technique is deduced directly by the Moore–Penrose generalized inverse of sensitivity matrix under the differential quotient rule of composite function. It can not only make the analysis process more effective but also analyze the noise influence on both frequencies and mode shapes in a similar way. Furthermore, an improved modal sensitivity based damage detection method is also proposed and compared with other two commonly used sensitivity-based methods in this paper. A one-story portal frame is adopted to evaluate the efficiency of both the proposed noise analysis technique and the improved modal sensitivity based method. The assessment results show that the proposed statistics-based noise analysis technique is effective and more suitable for the vibration-based damage identification. The improved modal sensitivity based method is more robust to noise than the other commonly used sensitivity-based methods.

scholarly journals A temperature-controlled cold-gas humidifier and its application to protein crystals with the humid-air and glue-coating method

2019 ◽  
Vol 52 (4) ◽  
pp. 699-705 ◽  
Author(s):  
Seiki Baba ◽  
Atsuhiro Shimada ◽  
Nobuhiro Mizuno ◽  
Junpei Baba ◽  
Hideo Ago ◽  
...  
Keyword(s):  
Protein Structures ◽  
Protein Crystal ◽  
Temperature Sensitive ◽  
Temperature Dependent ◽  
Humid Air ◽  
Ambient Temperatures ◽  
Highly Sensitive ◽  
Structural Differences ◽  
Coating Method ◽  
The Stability

The room-temperature experiment has been revisited for macromolecular crystallography. Despite being limited by radiation damage, such experiments reveal structural differences depending on temperature, and it is expected that they will be able to probe structures that are physiologically alive. For such experiments, the humid-air and glue-coating (HAG) method for humidity-controlled experiments is proposed. The HAG method improves the stability of most crystals in capillary-free experiments and is applicable at both cryogenic and ambient temperatures. To expand the thermal versatility of the HAG method, a new humidifier and a protein-crystal-handling workbench have been developed. The devices provide temperatures down to 4°C and successfully maintain growth at that temperature of bovine cytochrome c oxidase crystals, which are highly sensitive to temperature variation. Hence, the humidifier and protein-crystal-handling workbench have proved useful for temperature-sensitive samples and will help reveal temperature-dependent variations in protein structures.

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