scholarly journals Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

2020 ◽  
Vol 21 (18) ◽  
pp. 6530
Author(s):  
Jie Sheng ◽  
Nick K. Olrichs ◽  
Bart M. Gadella ◽  
Dora V. Kaloyanova ◽  
J. Bernd Helms
Keyword(s):  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Secretory Proteins ◽  
Functional Protein ◽  
Pathogenesis Related ◽  
Functional Amyloids ◽  
Related Proteins ◽  
Antigen 5 ◽  
Group 1

The idea that amyloid fibrils and other types of protein aggregates are toxic for cells has been challenged by the discovery of a variety of functional aggregates. However, an identification of crucial differences between pathological and functional aggregation remains to be explored. Functional protein aggregation is often reversible by nature in order to respond properly to changing physiological conditions of the cell. In addition, increasing evidence indicates that fast fibril growth is a feature of functional amyloids, providing protection against the long-term existence of potentially toxic oligomeric intermediates. It is becoming clear that functional protein aggregation is a complexly organized process that can be mediated by a multitude of biomolecular factors. In this overview, we discuss the roles of diverse biomolecules, such as lipids/membranes, glycosaminoglycans, nucleic acids and metal ions, in regulating functional protein aggregation. Our studies on the protein GAPR-1 revealed that several of these factors influence the amyloidogenic properties of this protein. These observations suggest that GAPR-1, as well as the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related proteins group 1 (CAP) superfamily of proteins that it belongs to, require the assembly into an amyloid state to exert several of their functions. A better understanding of functional aggregate formation may also help in the prevention and treatment of amyloid-related diseases.

scholarly journals Protein Co-Aggregation Related to Amyloids: Methods of Investigation, Diversity, and Classification

2018 ◽  
Vol 19 (8) ◽  
pp. 2292 ◽  
Author(s):  
Stanislav Bondarev ◽  
Kirill Antonets ◽  
Andrey Kajava ◽  
Anton Nizhnikov ◽  
Galina Zhouravleva
Keyword(s):  
Binding Site ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Specific Binding ◽  
Protein S ◽  
Functional Protein ◽  
Functional Roles ◽  
Protein Fibrils ◽  
Protein Functions ◽  
Functional Amyloids

Amyloids are unbranched protein fibrils with a characteristic spatial structure. Although the amyloids were first described as protein deposits that are associated with the diseases, today it is becoming clear that these protein fibrils play multiple biological roles that are essential for different organisms, from archaea and bacteria to humans. The appearance of amyloid, first of all, causes changes in the intracellular quantity of the corresponding soluble protein(s), and at the same time the aggregate can include other proteins due to different molecular mechanisms. The co-aggregation may have different consequences even though usually this process leads to the depletion of a functional protein that may be associated with different diseases. The protein co-aggregation that is related to functional amyloids may mediate important biological processes and change of protein functions. In this review, we survey the known examples of the amyloid-related co-aggregation of proteins, discuss their pathogenic and functional roles, and analyze methods of their studies from bacteria and yeast to mammals. Such analysis allow for us to propose the following co-aggregation classes: (i) titration: deposition of soluble proteins on the amyloids formed by their functional partners, with such interactions mediated by a specific binding site; (ii) sequestration: interaction of amyloids with certain proteins lacking a specific binding site; (iii) axial co-aggregation of different proteins within the same amyloid fibril; and, (iv) lateral co-aggregation of amyloid fibrils, each formed by different proteins.

The functions of CAP superfamily proteins in mammalian fertility and disease

2020 ◽  
Vol 26 (5) ◽  
pp. 689-723 ◽  
Author(s):  
Avinash S Gaikwad ◽  
Jinghua Hu ◽  
David G Chapple ◽  
Moira K O’Bryan
Keyword(s):  
Ion Channel ◽  
Protein Function ◽  
Cancer Biology ◽  
Rapid Evolution ◽  
Lipid Binding ◽  
Secretory Proteins ◽  
Protease Inhibition ◽  
Pubmed Database ◽  
Pathogenesis Related ◽  
Antigen 5

Abstract BACKGROUND Members of the cysteine-rich secretory proteins (CRISPS), antigen 5 (Ag5) and pathogenesis-related 1 (Pr-1) (CAP) superfamily of proteins are found across the bacterial, fungal, plant and animal kingdoms. Although many CAP superfamily proteins remain poorly characterized, over the past decade evidence has accumulated, which provides insights into the functional roles of these proteins in various processes, including fertilization, immune defence and subversion, pathogen virulence, venom toxicology and cancer biology. OBJECTIVE AND RATIONALE The aim of this article is to summarize the current state of knowledge on CAP superfamily proteins in mammalian fertility, organismal homeostasis and disease pathogenesis. SEARCH METHODS The scientific literature search was undertaken via PubMed database on all articles published prior to November 2019. Search terms were based on following keywords: ‘CAP superfamily’, ‘CRISP’, ‘Cysteine-rich secretory proteins’, ‘Antigen 5’, ‘Pathogenesis-related 1’, ‘male fertility’, ‘CAP and CTL domain containing’, ‘CRISPLD1’, ‘CRISPLD2’, ‘bacterial SCP’, ‘ion channel regulator’, ‘CatSper’, ‘PI15’, ‘PI16’, ‘CLEC’, ‘PRY proteins’, ‘ASP proteins’, ‘spermatogenesis’, ‘epididymal maturation’, ‘capacitation’ and ‘snake CRISP’. In addition to that, reference lists of primary and review article were reviewed for additional relevant publications. OUTCOMES In this review, we discuss the breadth of knowledge on CAP superfamily proteins with regards to their protein structure, biological functions and emerging significance in reproduction, health and disease. We discuss the evolution of CAP superfamily proteins from their otherwise unembellished prokaryotic predecessors into the multi-domain and neofunctionalized members found in eukaryotic organisms today. At least in part because of the rapid evolution of these proteins, many inconsistencies in nomenclature exist within the literature. As such, and in part through the use of a maximum likelihood phylogenetic analysis of the vertebrate CRISP subfamily, we have attempted to clarify this confusion, thus allowing for a comparison of orthologous protein function between species. This framework also allows the prediction of functional relevance between species based on sequence and structural conservation. WIDER IMPLICATIONS This review generates a picture of critical roles for CAP proteins in ion channel regulation, sterol and lipid binding and protease inhibition, and as ligands involved in the induction of multiple cellular processes.

scholarly journals The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins—Roles in Reproduction, Cancer, and Immune Defense

2008 ◽  
Vol 29 (7) ◽  
pp. 865-897 ◽  
Author(s):  
Gerard M. Gibbs ◽  
Kim Roelants ◽  
Moira K. O'Bryan
Keyword(s):  
Reproductive Tract ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mannose Receptor ◽  
Branching Morphogenesis ◽  
Immune Defense ◽  
Secretory Proteins ◽  
Pathogenesis Related ◽  
Peptidase Inhibitor ◽  
Antigen 5

Abstract The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences.

scholarly journals Induction of Pathogenesis-Related Proteins of Group 1 by Systemic Virus Infections of Nicotiana tabacum L.

1998 ◽  
Vol 18 (2) ◽  
pp. 63-70
Author(s):  
C Röhring
Keyword(s):  
Mosaic Virus ◽  
Potato Virus ◽  
Pr Proteins ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Protein ◽  
Virus Infections ◽  
Pathogenesis Related Proteins ◽  
Pathogenesis Related ◽  
Related Proteins ◽  
Group 1

AbstractThe induction of acid pathogenesis-related proteins (PR-proteins) of group 1 (PR-1) by systemic virus infections of tobacco plants was investigated during a time period between 3 and 19 days after inoculation. Each leaf position was investigated separately. The PR proteins were detected electrophoretically and, in addition, virus protein was detected by Enzyme Linked Immunosorbent Assay (ELISA). Potato virus X (PVX) and potato virus Y (PVY) were found to highly induce PR proteins in N. tabacum L. “Samsun NN”. The same results were obtained when PVX was investigated in N. tabacum L. “Samsun”. The accumulation started later and took place more slowly than during hypersensitive host reaction (HR) of “Samsun NN” to tobacco mosaic virus (TMV). A correlation was found between the accumulation of PR proteins and the accumulation of the virus in the same leaf. Cucumber mosaic virus (CMV) was less effective in PR protein induction than PVX and PVY. Consequently it could be demonstrated that PR proteins do not only appear due to hypersensitive host reactions but also during systemic virus infections.

scholarly journals Genetic Improvement for Resistance to Black Sigatoka in Bananas: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Julianna M. S. Soares ◽  
Anelita J. Rocha ◽  
Fernanda S. Nascimento ◽  
Adriadna S. Santos ◽  
Robert N. G. Miller ◽  
...  
Keyword(s):  
Genetic Improvement ◽  
Sub Saharan Africa ◽  
Black Sigatoka ◽  
Sources Of Resistance ◽  
Resistance Response ◽  
Pathogenesis Related ◽  
Improvement Programs ◽  
Sub Saharan ◽  
Related Proteins

Bananas are an important staple food crop in tropical and subtropical regions in Asia, sub-Saharan Africa, and Central and South America. The plant is affected by numerous diseases, with the fungal leaf disease black Sigatoka, caused by Mycosphaerella fijiensis Morelet [anamorph: Pseudocercospora fijiensis (Morelet) Deighton], considered one of the most economically important phytosanitary problem. Although the development of resistant cultivars is recognized as most effective method for long term control of the disease, the majority of today's cultivars are susceptible. In order to gain insights into this pathosystem, this first systematic literature review on the topic is presented. Utilizing six databases (PubMed Central, Web of Science, Google Academic, Springer, CAPES and Scopus Journals) searches were performed using pre-established inclusion and exclusion criteria. From a total of 3,070 published studies examined, 24 were relevant with regard to the Musa-P. fijiensis pathosystem. Relevant papers highlighted that resistant and susceptible cultivars clearly respond differently to infection by this pathogen. M. acuminata wild diploids such as Calcutta 4 and other diploid cultivars can harbor sources of resistance genes, serving as parentals for the generation of improved diploids and subsequent gene introgression in new cultivars. From the sequenced reference genome of Musa acuminata, although the function of many genes in the genome still require validation, on the basis of transcriptome, proteome and biochemical data, numerous candidate genes and molecules have been identified for further evaluation through genetic transformation and gene editing approaches. Genes identified in the resistance response have included those associated with jasmonic acid and ethylene signaling, transcription factors, phenylpropanoid pathways, antioxidants and pathogenesis-related proteins. Papers in this study also revealed gene-derived markers in Musa applicable for downstream application in marker assisted selection. The information gathered in this review furthers understanding of the immune response in Musa to the pathogen P. fijiensis and is relevant for genetic improvement programs for bananas and plantains for control of black Sigatoka.

scholarly journals Prognostic value of mitral regurgitation in patients with asymmetric hypertrophic cardiomyopathy

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Tesic ◽  
L Travica ◽  
V Giga ◽  
D Trifunovic ◽  
I Jovanovic ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Prognostic Value ◽  
Volume Index ◽  
Common Finding ◽  
Adequate Treatment ◽  
Group 2 ◽  
Group 1

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Since mitral regurgitation (MR) is a very common finding in patients with hypertrophic cardiomyopathy (HCM), the evaluation of the mitral valve anatomy and the degree of MR is of utmost importance in this population. However, data regarding the prognostic value of different degrees of MR in HCM remains scarce. Purpose The aim of this study was to determine whether the presence of a higher degree of MR affects: 1) long term prognosis; 2) clinical and echocardiographic presentation of HCM patients. Material and Methods We included prospectively 102 patients, diagnosed with primary asymmetric HCM. The degree of MR was determined echocardiographicaly according to current recommendations of the American Association of Echocardiography. According to the MR severity, patients were divided into 2 groups: Group 1 (n = 52) with no/trace or mild MR and Group 2 with moderate or moderate to severe MR. All patients had clinical and echocardiographic examination, 24-hour Holter ECG and NT pro BNP analysis performed. The primary outcome was a composite of: 1) HCM related death or sudden death; 2) hospitalization due to acute heart failure; 3) sustained ventricular tachycardia; 4) ischemic stroke. Results Patients with higher MR degree had more frequent chest pain (p = 0.039), syncope (p = 0.041) and NYHA II functional class (p < 0.001). Group 2 patients had mostly obstructive form of HCM (p < 0.001) with more frequent presence of previous atrial fibrillation (AF) (p = 0.032), as well as the new onset of AF (p = 0.014) compared to patients in Group 1. Patients with higher MR degree had significantly more SAM (p < 0.001) resulting in a more frequent eccentric MR jet (p < 0.001), along with calcified mitral annulus (p = 0.007), enlarged left atrial volume index (p < 0.001), and elevated right ventricular pressure (p = 0.001). As a result of higher MR grade, Group 2 had higher E/e" values (p < 0.001), elevated LV filling pressure (lateral E/e’ >10), as well as higher levels of NT pro BNP (p = 0.001). By Kaplan-Meier analysis we demonstrated that the event free survival rate during follow up of median 75 (IQR 48-103) months was significantly higher in Group 1 compared to the Group 2 (79% vs. 46%, p < 0.001), Figure 1. After adjustment for relevant confounders, moderate/moderate to severe MR remained as an independent predictor of adverse outcome (hazard ratio 2.58, 95% CI: 1.08-6.13, p < 0.001). Conclusion Presence of moderate, or moderate to severe MR was associated with poor long-term outcome of HCM patients. These results indicate the importance of an adequate MR assessment and detailed evaluation of the mitral valve anatomy in the prediction of complications and adequate treatment of patients with HCM. Abstract Figure.

scholarly journals Longitudinal Reproducibility of CO2-Triggered BOLD MRI for the Hemodynamic Evaluation of Adult Patients with Moyamoya Angiopathy

2021 ◽  
pp. 1-7
Author(s):  
Constantin Roder ◽  
Uwe Klose ◽  
Helene Hurth ◽  
Cornelia Brendle ◽  
Marcos Tatagiba ◽  
...  
Keyword(s):  
Intraclass Correlation ◽  
Collateral Flow ◽  
Surgical Revascularization ◽  
Bold Mri ◽  
Promising Tool ◽  
Hemodynamic Evaluation ◽  
Group 2 ◽  
Group 1

<b><i>Background and Purpose:</i></b> Hemodynamic evaluation of moyamoya patients is crucial to decide the treatment strategy. Recently, CO<sub>2</sub>-triggered BOLD MRI has been shown to be a promising tool for the hemodynamic evaluation of moyamoya patients. However, the longitudinal reliability of this technique in follow-up examinations is unknown. This study aims to analyze longitudinal follow-up data of CO<sub>2</sub>-triggered BOLD MRI to prove the reliability of this technique for long-term control examinations in moyamoya patients. <b><i>Methods:</i></b> Longitudinal CO<sub>2</sub> BOLD MRI follow-up examinations of moyamoya patients with and without surgical revascularization have been analyzed for all 6 vascular territories retrospectively. If revascularization was performed, any directly (by the disease or the bypass) or indirectly (due to change of collateral flow after revascularization) affected territory was excluded based on angiography findings (group 1). In patients without surgical revascularization between the MRI examinations, all territories were analyzed (group 2). <b><i>Results:</i></b> Eighteen moyamoya patients with 39 CO<sub>2</sub> BOLD MRI examinations fulfilled the inclusion criteria. The median follow-up between the 2 examinations was 12 months (range 4–29 months). For 106 vascular territories analyzed in group 1, the intraclass correlation coefficient was 0.784, <i>p</i> &#x3c; 0.001, and for group 2 (84 territories), it was 0.899, <i>p</i> &#x3c; 0.001. Within the total follow-up duration of 140 patient months, none of the patients experienced a new stroke. <b><i>Conclusions:</i></b> CO<sub>2</sub> BOLD MRI is a promising tool for mid- and long-term follow-up examinations of cerebral hemodynamics in moyamoya patients. Systematic prospective evaluation is required prior to making it a routine examination.

scholarly journals Current Understanding of the Structure, Stability and Dynamic Properties of Amyloid Fibrils

2021 ◽  
Vol 22 (9) ◽  
pp. 4349
Author(s):  
Eri Chatani ◽  
Keisuke Yuzu ◽  
Yumiko Ohhashi ◽  
Yuji Goto
Keyword(s):  
Amyloid Fibrils ◽  
Polypeptide Chain ◽  
Dynamic Properties ◽  
Protein Molecule ◽  
Side Chain ◽  
Structure Stability ◽  
Side Chains ◽  
Precise Control ◽  
Functional Amyloids ◽  
Structural Architecture

Amyloid fibrils are supramolecular protein assemblies represented by a cross-β structure and fibrous morphology, whose structural architecture has been previously investigated. While amyloid fibrils are basically a main-chain-dominated structure consisting of a backbone of hydrogen bonds, side-chain interactions also play an important role in determining their detailed structures and physicochemical properties. In amyloid fibrils comprising short peptide segments, a steric zipper where a pair of β-sheets with side chains interdigitate tightly is found as a fundamental motif. In amyloid fibrils comprising longer polypeptides, each polypeptide chain folds into a planar structure composed of several β-strands linked by turns or loops, and the steric zippers are formed locally to stabilize the structure. Multiple segments capable of forming steric zippers are contained within a single protein molecule in many cases, and polymorphism appears as a result of the diverse regions and counterparts of the steric zippers. Furthermore, the β-solenoid structure, where the polypeptide chain folds in a solenoid shape with side chains packed inside, is recognized as another important amyloid motif. While side-chain interactions are primarily achieved by non-polar residues in disease-related amyloid fibrils, the participation of hydrophilic and charged residues is prominent in functional amyloids, which often leads to spatiotemporally controlled fibrillation, high reversibility, and the formation of labile amyloids with kinked backbone topology. Achieving precise control of the side-chain interactions within amyloid structures will open up a new horizon for designing useful amyloid-based nanomaterials.

An ER–Golgi Tethering Factor SLOH4/MIP3 Is Involved in Long-term Heat Tolerance of Arabidopsis

2020 ◽  
Author(s):  
Kazuho Isono ◽  
Ryo Tsukimoto ◽  
Satoshi Iuchi ◽  
Akihisa Shinozawa ◽  
Izumi Yotsui ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Tolerance ◽  
Secretory Proteins ◽  
Wild Type ◽  
Additional Function ◽  
Transcript Levels ◽  
Unfolded Protein ◽  
In The Wild ◽  
Protein Response

Abstract Plants are often exposed not only to short-term (S-) heat stress but also to diurnal long-term (L-) heat stress over several consecutive days. To reveal the mechanisms underlying L-heat stress tolerance, we here used a forward genetic screening for sensitive to long-term heat (sloh) mutants and isolated sloh4. The mutant was hypersensitive to L- but not S-heat stress. The causal gene of sloh4 was identical to MIP3 encoding a member of the MAIGO2 (MAG2) tethering complex, which is composed of the MAG2, MIP1, MIP2, and MIP3 subunits and is localized at the endoplasmic reticulum (ER) membrane. Although sloh4/mip3 was hypersensitive to L-heat stress, the sensitivity of the mag2-3 and mip1–1 mutants was similar to that of the wild type. Under L-heat stress, the ER stress and the following unfolded protein response (UPR) were more pronounced in sloh4 than in the wild type. Transcript levels of bZIP60-regulated UPR genes were strongly increased in sloh4 under L-heat stress. Two processes known to be mediated by INOSITOL REQUIRING ENZYME1 (IRE1)—accumulation of the spliced bZIP60 transcript and a decrease in the transcript levels of PR4 and PRX34, encoding secretory proteins—were observed in sloh4 in response to L-heat stress. These findings suggest that misfolded proteins generated in sloh4 under L-heat stress may be recognized by IRE1 but not bZIP28, resulting in initiation of the UPR via activated bZIP60. Therefore, it would be possible that only MIP3 in MAG2 complex has an additional function in L-heat tolerance, which is not related to the ER–Golgi vesicle tethering.

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