scholarly journals A biuret‐derived, MS‐cleavable cross‐linking reagent for protein structural analysis: A proof‐of‐principle study

2019 ◽  
Vol 55 (1) ◽  
Author(s):  
Christoph Hage ◽  
Claudio Iacobucci ◽  
Michael Götze ◽  
Andrea Sinz
Keyword(s):  
Structural Analysis ◽  
Cross Linking ◽  
Protein Structural Analysis ◽  
Proof Of Principle

scholarly journals Vaccine candidate P6 of nontypable Haemophilus influenzae is not a transmembrane protein based on protein structural analysis

Vaccine ◽  
2011 ◽  
Vol 29 (8) ◽  
pp. 1624-1627 ◽  
Author(s):  
Lea Vacca Michel ◽  
Breanna Kalmeta ◽  
Mark McCreary ◽  
Joy Snyder ◽  
Paul Craig ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Haemophilus Influenzae ◽  
Vaccine Candidate ◽  
Transmembrane Protein ◽  
Protein Structural Analysis

scholarly journals Integrating population variation and protein structural analysis to improve the clinical genetic diagnosis and treatment in children with congenital nephrogenic diabetes insipidus

2020 ◽  
Author(s):  
Panli LIAO ◽  
Tianchao XIANG ◽  
Hongxia LI ◽  
Ye FANG ◽  
Xiaoyan FANG ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Isotonic Saline ◽  
Population Variation ◽  
Pathogenic Mutations ◽  
Protein Structural Analysis ◽  
Congenital Nephrogenic Diabetes Insipidus

Abstract Background and Objectives: Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. Establishing the genetic diagnosis appears particularly important to NDI for early detection and differential diagnosis.Method: We utilized a Chinese multicenter registry to investigate genotype and phenotype in children with NDI from 2014 to 2019. The structural locations of the pathogenic mutations from this study and the literature, as well as population variants retried from gnomAD were analyzed. Results: A total of 10 boys from 9 families carried mutations in AVPR2 (8/10) or AQP2 (2/10). Another 7 relatives of the families were diagnosed by sequencing for partial or subclinical NDI. Patients presented with dehydration, polyuria-polydipsia, and severe hypernatremia with a median age at diagnosis of 1.0 month (IQR 0.16, 18). Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane regions of AVPR2, and enrichment of diagnostic mutations by autosomal dominant inheritance (AD) in the C terminal region of AQP2. The pathogenic mutations are significantly more likely to be buried inside the domain comparing the population variants. Through structural analysis and in silico prediction, the eight mutations identified in this study were considered as presumably disease causative. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment of hypernatremic dehydration in neonates should not choose the isotonic saline as a rehydration fluid.Conclusion: Genetic analysis presumably confirmed the diagnosis of NDI in every patient of the studied cohort. A plea of early identifying NDI confirmed by phenotype and genotype, and consequently optimize the treatment.

scholarly journals Sorting of cadherin–catenin-associated proteins into individual clusters

2021 ◽  
Vol 118 (29) ◽  
pp. e2105550118
Author(s):  
Regina B. Troyanovsky ◽  
Alina P. Sergeeva ◽  
Indrajyoti Indra ◽  
Chi-Shuo Chen ◽  
Rei Kato ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Structural Unit ◽  
Force Sensing ◽  
Signaling Networks ◽  
Cross Linking ◽  
Cytoplasmic Proteins ◽  
Classical Cadherins ◽  
Cytoplasmic Tails ◽  
Associated Proteins ◽  
Proof Of Principle

The cytoplasmic tails of classical cadherins form a multiprotein cadherin–catenin complex (CCC) that constitutes the major structural unit of adherens junctions (AJs). The CCC in AJs forms junctional clusters, “E clusters,” driven by cis and trans interactions in the cadherin ectodomain and stabilized by α-catenin–actin interactions. Additional proteins are known to bind to the cytoplasmic region of the CCC. Here, we analyze how these CCC-associated proteins (CAPs) integrate into cadherin clusters and how they affect the clustering process. Using a cross-linking approach coupled with mass spectrometry, we found that the majority of CAPs, including the force-sensing protein vinculin, interact with CCCs outside of AJs. Accordingly, structural modeling shows that there is not enough space for CAPs the size of vinculin to integrate into E clusters. Using two CAPs, scribble and erbin, as examples, we provide evidence that these proteins form separate clusters, which we term “C clusters.” As proof of principle, we show, by using cadherin ectodomain monoclonal antibodies (mAbs), that mAb-bound E-cadherin forms separate clusters that undergo trans interactions. Taken together, our data suggest that, in addition to its role in cell–cell adhesion, CAP-driven CCC clustering serves to organize cytoplasmic proteins into distinct domains that may synchronize signaling networks of neighboring cells within tissues.

scholarly journals Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity

2020 ◽  
Author(s):  
Takuma Hayashi ◽  
Nobuo Yaegashi ◽  
Ikuo Konishi
Keyword(s):  
Experimental Study ◽  
Monoclonal Antibodies ◽  
Natural Selection ◽  
Structural Analysis ◽  
Growth Process ◽  
Three Dimensional ◽  
Neutralizing Antibody ◽  
Antibody Affinity ◽  
Protein Structural Analysis

AbstractNatural selection “adaptation” in the coronavirus can occur during coronavirus amplification in vivo in farmed minks. Natural selection in such viruses is observed by introduction of mutations in SARS- CoV-2 that are not observed during the growth process in humans. Infection with a mutant (Y453F) of SARS-CoV-2 from farmed minks is known to widely spread among humans. We investigated the virological characteristics of this SARS-CoV-2 mutant (Y453F) using three-dimensional protein structural analysis. Our experimental study suggests that virus variants with the Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies. The spread of SARS-CoV-2 variants mediated by millions of infected farmed minks is uncontrolled; consequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.

scholarly journals Developing a Multiplexed Quantitative Cross-Linking Mass Spectrometry Platform for Comparative Structural Analysis of Protein Complexes

2016 ◽  
Vol 88 (20) ◽  
pp. 10301-10308 ◽  
Author(s):  
Clinton Yu ◽  
Alexander Huszagh ◽  
Rosa Viner ◽  
Eric J. Novitsky ◽  
Scott D. Rychnovsky ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Structural Analysis ◽  
Protein Complexes ◽  
Cross Linking
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