GA/GB Fold switching may modulate fatty acid transfer from human serum albumin to bacteria

Polticelli, Fabio; Caprari, Silvia; Gianni, Stefano; Ascenzi, Paolo

doi:10.1002/iub.1083

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…toward C. difficile TcdA and TcdB (25,26) and S. pyogenes SLO toxins (data here reported), binding of HSA to the GA module of F. magna could provide growing bacteria with FAs and, possibly, other nutrients transported by HSA (52,53). Overall, the selective recognition of bacteria proteins and toxins through domain II of HSA represents a clear example of host-microbe adaptation at the molecular level.…”

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confidence: 51%

Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Vita

Leboffe

et al. 2020

Front. Immunol.

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The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity “orchestra.” We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing Clostridioides difficile toxins that reach the bloodstream after being produced in the colon. Here, we report the in vitro and ex vivo capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with C. difficile toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system.

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confidence: 51%

Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Vita

Leboffe

et al. 2020

Front. Immunol.

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“…41 , 42 This protein provides selective advantages to the bacterium, delivering FAs and other nutrients transported by HSA. 41 , 43 …”

Section: The Hsa Structural Organizationmentioning

confidence: 99%

Heme-based catalytic properties of human serum albumin

Ascenzi

Masi

Fanali

et al. 2015

Cell Death Discovery

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Human serum albumin (HSA): (i) controls the plasma oncotic pressure, (ii) modulates fluid distribution between the body compartments, (iii) represents the depot and carrier of endogenous and exogenous compounds, (iv) increases the apparent solubility and lifetime of hydrophobic compounds, (v) affects pharmacokinetics of many drugs, (vi) inactivates toxic compounds, (vii) induces chemical modifications of some ligands, (viii) displays antioxidant properties, and (ix) shows enzymatic properties. Under physiological and pathological conditions, HSA has a pivotal role in heme scavenging transferring the metal-macrocycle from high- and low-density lipoproteins to hemopexin, thus acquiring globin-like reactivity. Here, the heme-based catalytic properties of HSA are reviewed and the structural bases of drug-dependent allosteric regulation are highlighted.

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“…The possibility that highly homologous proteins may display different folds and functions agrees with the interchangeable structural organization of the all‐α GA module of the bacterial protein PAB with that of the 4β+α GB domain, the conformational switch depending on a single amino acid substitution . Moreover, the GA module has been hypothesized to interconvert to the structure typical of the GB domain upon fatty acid binding, as part of the mechanism, which allows the bacterial PAB protein to extract fatty acids from human serum albumin .…”

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confidence: 86%

Different disulfide bridge connectivity drives alternative folds in highly homologousBrassicaceaetrypsin inhibitors

et al. 2015

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Low-molecular-mass trypsin inhibitors from Arabidopsis thaliana, Brassica napus var. oleifera, and Sinapis alba L. (ATTI, RTI, and MTI, respectively) display more than 69% amino acid sequence identity. Among others, the amino acid sequence Cys-Ala-Pro-Arg-Ile building up the inhibitor reactive site, and the eight Cys residues forming four disulfide bridges are conserved. However, the disulfide bridge connectivity of RTI and MTI (C 1 -C 3 , C 2 -C 4 , C 5 -C 6 , and C 7 -C 8 ) is different from that of ATTI Cys (C 1 -C 8 , C 2 -C 5 , C 3 -C 6 , and C 4 -C 7 ). Despite the different disulfide bridge connectivity, the reactive site loop of ATTI, RTI, and MTI is solvent exposed permitting trypsin recognition. Structural considerations here reported suggest that proteins showing high amino acid sequence identity and common functional properties could display different threedimensional structures. This may reflect high inhibitor plasticity in relation to plant-pathogen interactions, plant tissue development as well as the different redox potential of cell compartments. V C 2015 IUBMB Life, 67(12): [966][967][968][969][970] 2015 Keywords: plant trypsin inhibitors; disulfide bridge connectivity; primary structure; three-dimensional structure; Arabidopsis thaliana; Brassica napus var. oleifera; Sinapis alba L Serine proteinase inhibitors are widespread in the plant kingdom, their physiological roles including the regulation of endogenous proteinases during seed dormancy, the mobilization of protein reserves, the protection against the proteolytic enzymes of parasites and insects, and anti-metabolic effects leading to inhibition of larval growth (1,2). Moreover, protein serine proteinase inhibitors may also act as storage or reserve proteins. The occurrence of serine proteinase inhibitors belonging to different families in the same plant suggests that these proteins have evolved separately to perform distinct physiological roles (2-4). Moreover, a fractional heterogeneity has been observed even within a specific class of serine proteinase inhibitors as in the case of Pin-II/Pot-II family that displays a remarkable structural and functional diversity (5,6).Plant serine proteinase inhibitors, found mainly in seeds of Brassicaceae, Poaceae, and Leguminosae as well as in tubers of Solanaceae, are grouped into the Soybean (Kunitz), Bowman-Birk, potato I and II, squash, barley, ragi 1 and 2, RTI/MTI, and thaumatin families, according to their chemical and biological features (2,3,7-11).Abbreviations: ATTI, putative low-molecular-mass trypsin inhibitor mapped in the chromosome II of Arabidopsis thaliana; BPTI, bovine basic pancreatic trypsin inhibitor; MTI, low-molecular-mass trypsin inhibitor type-2A from white mustard (Sinapis alba L.) seeds; RTI, low-molecular-mass trypsin inhibitor type-III from oil-rape (Brassica napus var. oleifera) seeds.

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GA/GB Fold switching may modulate fatty acid transfer from human serum albumin to bacteria

Cited by 9 publications

References 25 publications

Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Heme-based catalytic properties of human serum albumin

Different disulfide bridge connectivity drives alternative folds in highly homologousBrassicaceaetrypsin inhibitors

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