scholarly journals A local α-helix drives structural evolution of streptococcal M-protein affinity for host human plasminogen

2020 ◽  
Vol 477 (9) ◽  
pp. 1613-1630
Author(s):  
Cunjia Qiu ◽  
Yue Yuan ◽  
Shaun W. Lee ◽  
Victoria A. Ploplis ◽  
Francis J. Castellino
Keyword(s):  
Tight Binding ◽  
Class Ii ◽  
Class I ◽  
M Protein ◽  
Class Iii ◽  
Streptococcal M Protein ◽  
Special Cases ◽  
Group A ◽  
Human Plasminogen ◽  
A Domains

Plasminogen-binding group A streptococcal M-protein (PAM) is a signature surface virulence factor of specific strains of Group A Streptococcus pyogenes (GAS) and is an important tight binding protein for human plasminogen (hPg). After activation of PAM-bound hPg to the protease, plasmin (hPm), GAS cells develop invasive surfaces that are critical for their pathogenicity. PAMs are helical dimers in solution, which are sensitive to temperature changes over a physiological temperature range. We previously categorized PAMs into three classes (I–III) based on the number and nature of short tandem α-helical repeats (a1 and a2) in their NH2-terminal A-domains that dictate interactions with hPg/hPm. Class II PAMs are special cases since they only contain the a2-repeat, while Class I and Class III PAMs encompass complete a1a2-repeats. All dimeric PAMs tightly associate with hPg, regardless of their categories, but monomeric Class II PAMs bind to hPg much weaker than their Class I and Class III monomeric counterparts. Additionally, since the A-domains of Class II PAMs comprise different residues from other PAMs, the issue emerges as to whether Class II PAMs utilize different amino acid side chains for interactions with hPg. Herein, through NMR-refined structural analyses, we elucidate the atomic-level hPg-binding mechanisms adopted by two representative Class II PAMs. Furthermore, we develop an evolutionary model that explains from unique structural perspectives why PAMs develop variable A-domains with regard to hPg-binding affinity.

scholarly journals Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever.

1989 ◽  
Vol 169 (1) ◽  
pp. 269-283 ◽  
Author(s):  
D Bessen ◽  
K F Jones ◽  
V A Fischetti
Keyword(s):  
Rheumatic Fever ◽  
Class Ii ◽  
Class I ◽  
M Protein ◽  
Repeat Region ◽  
Streptococcal M Protein ◽  
Antigenic Relatedness ◽  
M Proteins ◽  
Protein Molecules ◽  
Definition Of

The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever.

scholarly journals Outcome of Albumin Infusion in Heart Failure Patients

2019 ◽  
Vol 15 (2) ◽  
pp. 47-53
Author(s):  
Ashaduzzaman Talukder ◽  
Mohamed Mausool Siraj ◽  
Md Noornabi Khondokar ◽  
SM Ahsan Habib ◽  
Md Abu Salim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Serum Albumin ◽  
Nyha Class ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Albumin Infusion ◽  
Group A ◽  
Group B ◽  
Class Iv

Background: Heart Failure (HF) is a major public health burden worldwide. Approximately 5 million Americans, 0.4–2% of the general European population and over 23 million people worldwide are living with heart failure. Like few other chronic disease, low serum albumin is common in patients with heart failure (HF). However, very few studies evaluated the outcome of albumin infusion in different stages of HF. Therefore, the objective of this study is to assess the outcome of albumin infusion in heart failure patients. Methods: It was a cross-sectional study. A total of 50 cases of chronic heart failure with reduced ejection fraction and NYHA class III or IV with serum albumin level <2.5g/dl who were admitted in CCUwere selected by purposive sampling, from September 2017 to August 2018. 100ml of 20% albumin was infused and serum albumin was measured after 3 days. Then the patients were divided into two groups, Patients who failed to attain serum albumin of 3g/dl(Group A) or Patients who attained serum albumin of ≥3g/dl (Group B). Analysis and comparison for symptomatic improvement of heart failure by NHYA classification and LVEF was done at 10th day after infusion between group A and B. Result: Among the 50 patients, mean age of patients was 53.64 ± 13.44 years (age range: 26-84 years) with a male-female ratio of 3:2 (60%-male vs 40%- female). Majority patients were previously re-admitted at least two times (40%), 28% were re-admitted once, 16% were re-admitted three times and 4% were re-admitted for four times. Of all, 56% patients presented NYHA class IV and AHA stage D heart failure (56%) and 44% patients presented with NYHA class III and AHA stage C. At day 10 follow up following albumin infusion, overall frequency of following ten days of albumin therapy, in group B, 8 patients (72.7%) among Class III improved to Class I and 3 patients (27.3%) improved to class II. Also, 7 patients (50%), 5 patients (35.7%) and 2 patients (14.3%) among class IV improved to respectively class I, class II and class III. In group A, 3 patients (27.3%) among class III improve to class II and 8 patients (72.7%) remain in class III. Also, 2 patients (14.3%), 5 Patients (35.7%) and 7 patients (50%) among class IV improve to respectively class I, class II and class III. Moreover, statistically significant improvement was noted in ejection fraction of patents irrespective of initial class of heart failure (p<0.001) in group B patients compare to group A (p<0.09). Conclusion: In this study, the improvement of heart failure was more in patients who attained albumin level of ≥3g/dl.Therefore, in can be concluded that albumin infusion improves both subjective and objective improvement of patients with heart failure. University Heart Journal Vol. 15, No. 2, Jul 2019; 47-53

scholarly journals Binding of the kringle-2 domain of human plasminogen to streptococcal PAM-type M-protein causes dissociation of PAM dimers

2021 ◽  
Author(s):  
Olawole Ayinuola ◽  
Yetunde Ayinuola ◽  
Cunjia Qiu ◽  
Shaun Lee ◽  
Victoria Ploplis ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Tight Binding ◽  
Coiled Coil ◽  
M Protein ◽  
Temperature Dependent ◽  
Functional Monomers ◽  
Molecular Weights ◽  
Group A ◽  
Human Plasminogen ◽  
Kringle 2

M-protein (PAM) largely contributes to the pathogenesis of Pattern D Group A Streptococcus pyogenes (GAS). However, the mechanism of complex formation is unknown. In a system consisting of a Class II PAM from Pattern D GAS isolate NS88.2 (PAMNS88.2), with one K2hPg binding a-repeat in its A-domain, we employed biophysical techniques to analyze the mechanism of the K2hPg/PAMNS88.2 interaction. We show that apo-PAMNS88.2 is a coiled-coil homodimer (M.Wt. ~80 kDa) at 4°C - 25°C, and is monomeric (M.Wt. ~40 kDa) at 37°C, demonstrating a temperature-dependent dissociation of PAMNS88.2 over a narrow temperature range. PAMNS88.2 displayed a single tight binding site for K2hPg at 4°C, which progressively increased at 25°C through 37°C. We isolated the K2hPg/PAMNS88.2 complexes at 4°C, 25°C, and 37°C and found molecular weights of ~50 kDa at each temperature, corresponding to a 1:1 (m:m) K2hPg/PAMNS88.2 monomer complex. hPg activation experiments by streptokinase demonstrated that the hPg/PAMNS88.2 monomer complexes are fully functional. The data show that PAM dimers dissociate into functional monomers at physiological temperatures or when presented with the active hPg module (K2hPg) showing that PAM is a functional monomer at 37°C.

scholarly journals Class II Skeletal Malocclusion and Prevalence of Temporomandibular Disorders. An Epidemiological Pilot Study on Growing Subjects

2021 ◽  
Vol 6 (3) ◽  
pp. 63
Author(s):  
Grazia Fichera ◽  
Vincenzo Ronsivalle ◽  
Simona Santonocito ◽  
Khaled S. Aboulazm ◽  
Gaetano Isola ◽  
...  
Keyword(s):  
Temporomandibular Disorders ◽  
Class Ii ◽  
Class I ◽  
Class Ii Malocclusion ◽  
Class Iii ◽  
Predisposing Factor ◽  
Skeletal Malocclusion ◽  
Skeletal Class Ii ◽  
Group A ◽  
Male Subjects

The purpose of our work is to evaluate the correlation between skeletal Class II malocclusion and temporomandibular disorders, by assessing potential different frequency scores compared with Class I and Class III skeletal malocclusion, and to evaluate associated etiological and risk factors. Fifty-five subjects were examined, 35 females and 20 males, with a mean age of 18 ± 1.3 years, divided into two groups: those with TMD and those without TMD, and prevalence was evaluated in the two groups of Class II subjects. Symptoms and more frequent signs were also examined in the TMD group. Regarding Group A (subjects with the presence of TMD), we found that 48% have a Class II, 16% have Class I, and 28% have Class III. In the totality of the group A sample, only 8% were male subjects. In Group B (subjects without TMD), we found that 40% were females, with 26.7% in Class I, 10% in Class II, and 3.3% in Class III; the male subjects in this group (60%) were distributed with 33.3% in Class I, 16.7% in Class II, and 10% in Class III. Class II malocclusion is not a causal factor of TMD but may be considered a predisposing factor.

scholarly journals Superantigenicity of streptococcal M protein.

1990 ◽  
Vol 172 (1) ◽  
pp. 359-362 ◽  
Author(s):  
M Tomai ◽  
M Kotb ◽  
G Majumdar ◽  
E H Beachey
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
M Protein ◽  
Streptococcal M Protein ◽  
Human T Cells ◽  
M Proteins ◽  
Group A ◽  
Cell Mitogen ◽  
Antigen Presenting

M proteins that define the serotypes of group A streptococci are powerful blastogens for human T lymphocytes. The mechanism by which they activate T cells was investigated and compared with the conventional T cell mitogen phytohemagglutinin, and the known superantigen staphylococcal enterotoxin B. Although major histocompatibility complex (MHC) class II molecules are required for presentation, there is no MHC restriction, since allogeneic class II molecules presented the bacterial protein to human T cells. Type 5 M protein appears to bind class II molecules on the antigen-presenting cells and stimulate T cells bearing V beta 8 sequences. Our results indicate that this streptococcal M protein is a superantigen and suggest a possible mechanism of its role in the pathogenesis of the postinfectious autoimmune sequelae.

scholarly journals Immunological Relationship between the Class I Epitope of Streptococcal M Protein and Myosin

1998 ◽  
Vol 66 (9) ◽  
pp. 4418-4424 ◽  
Author(s):  
Anthony Quinn ◽  
Kent Ward ◽  
Vincent A. Fischetti ◽  
Mark Hemric ◽  
Madeleine W. Cunningham
Keyword(s):  
Coiled Coil ◽  
Class I ◽  
M Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acute Glomerulonephritis ◽  
Human Antibody ◽  
Streptococcal M Protein ◽  
Skeletal Myosin ◽  
Group A ◽  
Immunological Relationship

ABSTRACT The class I epitope of streptococcal M protein is an epidemiological marker for acute rheumatic fever (ARF)-associated serotypes of group A streptococci and is recognized by anti-M protein monoclonal antibody (MAb) 10B6. Using MAb 10B6, we determined the relationship between the class I epitope of M protein and the α-helical coiled-coil protein myosin. MAb 10B6 reacted by enzyme-linked immunosorbent assay and Western blotting with human cardiac myosin and rabbit skeletal myosin and its heavy meromyosin (HMM) subfragment. Overlapping synthetic peptides of M5 protein were used to identify the region of M5 protein recognized by MAb 10B6. Two C repeat peptides (C2A and C3) containing the amino acid sequence KGLRRDLDASREAK reacted with MAb 10B6. Partial sequence identity, RRDL, was found in the HMM fragment of myosin, which reacted with MAb 10B6. However, not all peptides of M5 protein and myosin containing the RRDL sequence reacted with MAb 10B6. ARF sera and sera from uncomplicated pharyngitis (UNC) reacted with C repeat region peptides of M protein, while acute glomerulonephritis sera were not as reactive. Affinity-purified human antibody to peptide C3 reacted with myosin. The data demonstrate that the class I epitope of M protein is immunologically cross-reactive with myosin and the HMM subfragment, and antibodies to peptide C3 and myosin were present in ARF and UNC sera.

scholarly journals Environmental Cadmium Exposure and Dental Indices in Orthodontic Patients

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 413
Author(s):  
Hui-Ling Chen ◽  
Jason Chen-Chieh Fang ◽  
Chia-Jung Chang ◽  
Ti-Feng Wu ◽  
I-Kuan Wang ◽  
...  
Keyword(s):  
Cadmium Concentration ◽  
Class Ii ◽  
Cadmium Exposure ◽  
Class I ◽  
P Value ◽  
Tooth Decay ◽  
Class Iii ◽  
Orthodontic Patients ◽  
Urine Cadmium ◽  
The Mean

Background. Previous studies have shown that environmental cadmium exposure could disrupt salivary gland function and is associated with dental caries and reduced bone density. Therefore, this cross-sectional study attempted to determine whether tooth decay with tooth loss following cadmium exposure is associated with some dental or skeletal traits such as malocclusions, sagittal skeletal pattern, and tooth decay. Methods. Between August 2019 and June 2020, 60 orthodontic patients with no history of previous orthodontics, functional appliances, or surgical treatment were examined. The patients were stratified into two groups according to their urine cadmium concentrations: high (>1.06 µg/g creatinine, n = 28) or low (<1.06 µg/g creatinine, n = 32). Results. The patients were 25.07 ± 4.33 years old, and most were female (female/male: 51/9 or 85%). The skeletal relationship was mainly Class I (48.3%), followed by Class II (35.0%) and Class III (16.7%). Class I molar relationships were found in 46.7% of these patients, Class II molar relationships were found in 15%, and Class III molar relationships were found in 38.3%. The mean decayed, missing, and filled surface (DMFS) score was 8.05 ± 5.54, including 2.03 ± 3.11 for the decayed index, 0.58 ± 1.17 for the missing index, and 5.52 ± 3.92 for the filled index. The mean index of complexity outcome and need (ICON) score was 53.35 ± 9.01. The facial patterns of these patients were within the average low margin (26.65 ± 5.53 for Frankfort–mandibular plane angle (FMA)). There were no significant differences in the above-mentioned dental indices between patients with high urine cadmium concentrations and those with low urine cadmium concentrations. Patients were further stratified into low (<27, n = 34), average (27–34, n = 23), and high (>34, n = 3) FMA groups. There were no statistically significant differences in the urine cadmium concentration among the three groups. Nevertheless, a marginally significant p-value of 0.05 for urine cadmium concentration was noted between patients with low FMA and patients with high FMA. Conclusion. This analysis found no association between environmental cadmium exposure and dental indices in our orthodontic patients.

scholarly journals A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe

1976 ◽  
Vol 159 (2) ◽  
pp. 245-257 ◽  
Author(s):  
R Norris ◽  
K Brocklehurst
Keyword(s):  
Convenient Method ◽  
Specific Activity ◽  
Class Ii ◽  
High Reactivity ◽  
Class I ◽  
Thiol Groups ◽  
Class Iii ◽  
Active Centre ◽  
Class Ib ◽  
Covalent Chromatography

1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 ± 1.47 kat/kg, Km = 3.32 ± 0.05 mM; kcat. = 2.15 × 104 ± 0.05 × 104s-1 at pH7.0 and 38°C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin.11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and ε280 = 2.84 × 105 litre·mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six ‘essential’ thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25°C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 × 104M-1·s-1 and (b) pKa = 8.1, k = 8.05 × 102M-1·s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 × 102M-1·s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases as the pH is raised according to a pKa value ≥ approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the ‘essential’ thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.

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