Mechanism for the homocysteine-enhanced antifibrinolytic potential of lipoprotein(a) in human plasma

2005 ◽  
Vol 94 (07) ◽  
pp. 75-81 ◽  
Author(s):  
Marina Nardulli ◽  
Vincent Durlach ◽  
Gabriella Pepe ◽  
Eduardo Anglés-Cano
Keyword(s):  
Human Plasma ◽  
Structure And Function ◽  
Plasma Homocysteine ◽  
Plasminogen Activation ◽  
Total Plasma ◽  
Lipoprotein A ◽  
High Affinity ◽  
Main Target ◽  
And Function ◽  
Acting In Concert

SummaryLipoprotein(a) and total plasma homocysteine levels are now established as independent atherothrombogenic risk factors. A distinctive pathophysiological feature of lipoprotein(a) is its antifibrinolytic activity, an effect dependent on plasma concentration and high affinity for fibrin of its small size apo(a) component. A stimulating effect of homocysteine on purified lipoprotein(a) has been proposed. However, little is known about their specific interactions in human plasma. We demonstrate by immunochemical, ligand-binding and plasminogen activation studies, that homocysteine modifies the structure and function of lipoprotein(a) in human plasma; it reduces the apo(a)/apoB disulfide bond causing the appearance of free apo(a) with high affinity for fibrin that inhibits plasminogen binding and plasmin formation (r= −0.995, p=0.002). These effects were evident particularly in plasma samples containing lipoprotein(a) with low affinity for fibrin and more than 22 kringles apo(a) isoforms. In contrast, for plasmas containing high fibrin affinity lipoprotein(a) (less than 22 kringles apo[a] isoforms) no significant change neither in fibrin binding nor in plasmin formation was observed. Furthermore, isolated apo(a) recombinants (10 to 34 kringles) that have been shown to display size-independent high affinity for fibrin were not affected by homocysteine, thus confirming lipoprotein(a) as its main target. These results suggest that the pro-atherogenic role already conferred to lipoprotein(a) by small apo(a) isoforms may be extended to large apo(a) isoforms if released in plasma by homocysteine, as this mechanism reveals their high fibrin affinity. Lipoprotein(a) and homocysteine may therefore constitute, if acting in concert, a new risk factor for athero-thrombotic vascular disease.

Structure and Function of P19, a High-Affinity Iron Transporter of the Human Pathogen Campylobacter jejuni

2010 ◽  
Vol 401 (4) ◽  
pp. 590-604 ◽  
Author(s):  
Anson C.K. Chan ◽  
Tzanko I. Doukov ◽  
Melanie Scofield ◽  
Stacey A.L. Tom-Yew ◽  
Alexander B. Ramin ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Structure And Function ◽  
Human Pathogen ◽  
High Affinity ◽  
Iron Transporter ◽  
And Function

scholarly journals Effect of cross-linkers on the structure and function of pig-renal sodium–glucose cotransporters after papain treatment

1998 ◽  
Vol 330 (2) ◽  
pp. 733-736 ◽  
Author(s):  
Jean GIUDICELLI ◽  
Marie-France BERTRAND ◽  
Stephane BILSKI ◽  
T. Than TRAN ◽  
Jean-Claude POIREE
Keyword(s):  
Binding Sites ◽  
Specific Inhibitor ◽  
Structure And Function ◽  
Scatchard Analysis ◽  
High Affinity ◽  
Phlorizin Binding ◽  
Sodium Dependent ◽  
Spacer Arm ◽  
Molecular Masses ◽  
And Function

Kidney brush-border membranes contain two sodium-dependent glucose transporters, one with low and one with high affinity for phlorizin, the specific inhibitor of these transporters. Using Scatchard analysis of phlorizin binding and Western blotting with specific antibodies against these transporters, we demonstrate in this study that although both transporters were proteolysed by papain treatment, only the high-affinity phlorizin-binding sites were decreased. Papain treatment followed by cross-linking with homobifunctional disuccinimidyl tartarate restored only the structure of the low-affinity phlorizin-binding protein (approx. molecular mass 70 kDa) without modifying the phlorizin-binding sites. When disuccinimidyl tartarate was replaced with dithiobis(succinimidyl acetate), another homobifunctional cross-linker with a higher spacer arm, the low- and high-affinity sites were both restored, with reappearance of two phlorizin-binding proteins with approx. molecular masses of 70 and 120 kDa. We conclude that high-affinity phlorizin-binding sites depend on the presence of the heterodimeric 120 kDa protein.

scholarly journals Global chemical modifications comparison of human plasma proteomes from two different age groups

2020 ◽  
Author(s):  
Yongtao Liu ◽  
Mindi Zhao ◽  
Xuanzhen Pan ◽  
Youhe Gao
Keyword(s):  
Amino Acid ◽  
Human Plasma ◽  
Age Groups ◽  
Young Group ◽  
Structure And Function ◽  
Plasma Proteome ◽  
Chemical Modifications ◽  
Old People ◽  
And Function ◽  
Human Plasma Proteome

AbstractThe chemical modification of proteins refers to the covalent group reaction involved in their amino acid residues or chain ends which, in turn, change the molecular structure and function of the proteins. There are many types of molecular modifications in the human plasma proteome, such as phosphorylation, methylation, and acetylation. In this study, two groups of human plasma proteome at different age groups (old and young) were used to perform a comparison of global chemical modifications, as determined by tandem mass spectrometry (MS/MS) combined with non-limiting modification identification algorithms. The sulfhydryl in the cysteine A total of 4 molecular modifications were found to have significant differences: the succinylation and phosphorylation modification of cysteine (Cys, C) and the modification of lysine (Lys, K) with threonine (Thr, T) were significantly higher in the old group than in the young group, while the carbamylation of lysine was lower in the young group. Cysteine residue is an important group for forming disulphide bonds and maintaining the structure of the protein. Differential cysteine-related sulfydryl modifications may cause structural and functional changes. Lysine is a basic amino acid, and the modification of its amino group will change the charge state of the protein, which may affect the structure and function of the protein. In summary, four types of protein chemical modifications and substitutes were found to be significantly different in the plasma proteome in different age groups and their probabilities of random generation are lower by passing random grouping test. We speculate that there is an increase in certain modified proteins in the blood of the old people which, in turn, changes the function of those proteins. This change may be one of the reasons why the old people are more likely than the young people to be at risk for age-related diseases, such as metabolic diseases, cerebral and cardiovascular diseases, and cancer.

Structure and Function of the Human Plasma Apolipoproteins

1980 ◽  
pp. 624-630 ◽  
Author(s):  
Henry J. Pownall ◽  
James T. Sparrow ◽  
Louis C. Smith ◽  
Antonio M. Gotto
Keyword(s):  
Human Plasma ◽  
Structure And Function ◽  
And Function

scholarly journals The ORF1 Protein Encoded by LINE-1: Structure and Function During L1 Retrotransposition

2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Sandra L. Martin
Keyword(s):  
Nucleic Acid ◽  
Reverse Transcriptase ◽  
Rna Binding ◽  
Early Recognition ◽  
Structure And Function ◽  
Predicted Amino Acid Sequence ◽  
Ribonucleoprotein Particle ◽  
High Affinity ◽  
Nucleic Acid Chaperone ◽  
And Function

LINE-1 or L1 is an autonomous non-LTR retrotransposon in mammals. Retrotransposition requires the function of the two L1-encoded polypeptides, ORF1p and ORF2p. Early recognition of regions of homology between the predicted amino acid sequence of ORF2 and known endonuclease and reverse transcriptase enzymes led to testable hypotheses regarding the function of ORF2p in retrotransposition. As predicted, ORF2p has been demonstrated to have both endonuclease and reverse transcriptase activities. In contrast, no homologs of known function have contributed to our understanding of the function of ORF1p during retrotransposition. Nevertheless, significant advances have been made such that we now know that ORF1p is a high-affinity RNA-binding protein that forms a ribonucleoprotein particle together with L1 RNA. Furthermore, ORF1p is a nucleic acid chaperone and this nucleic acid chaperone activity is required for L1 retrotransposition.

scholarly journals Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3373
Author(s):  
Ayaulym Bekbossynova ◽  
Albina Zharylgap ◽  
Olena Filchakova
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Structure And Function ◽  
Structural Determinants ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Marine Snails ◽  
And Function ◽  
Proteins And Peptides

Acetylcholine was the first neurotransmitter described. The receptors targeted by acetylcholine are found within organisms spanning different phyla and position themselves as very attractive targets for predation, as well as for defense. Venoms of snakes within the Elapidae family, as well as those of marine snails within the Conus genus, are particularly rich in proteins and peptides that target nicotinic acetylcholine receptors (nAChRs). Such compounds are invaluable tools for research seeking to understand the structure and function of the cholinergic system. Proteins and peptides of venomous origin targeting nAChR demonstrate high affinity and good selectivity. This review aims at providing an overview of the toxins targeting nAChRs found within venoms of different animals, as well as their activities and the structural determinants important for receptor binding.

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