PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 6579719

Plasma protein interactions at biological interfaces.

G V Seaman
View original source ↗Export metadata ↓

Abstract

The adsorption of plasma proteins, especially fibrinogen at the endoendothelial interface and to the surfaces of the blood cellular elements in contact with blood is relevant to both hemostasis and thrombogenesis. The intact endothelium is the most thrombo-resistant surface known and the exact nature of this structure holds the answer to developing adequate biocompatibility for implants and prosthetic devices. Under physiological conditions the endoendothelial surface, blood cellular elements and plasma proteins all possess net negative charges which will play a role in their interactions. The density and charge sign of ionizable surface groups will determine the local value of pH at that surface. Distributions of surface charge are possible which could lead to local pH values which vary from one region to another by several units of pH. Erythrocytes and platelets possess adsorbed fibrinogen and the endothelial surface is likely also to attract fibrinogen. The presence of one or more layers of fibrinogen on the endothelial lining is, therefore, a well founded physicochemical expectation. Aggregation of the blood cellular elements is mediated by calcium ions, fibrinogen and other agents depending upon the cell type. The presence of fibrinogen is essential for platelet aggregation induced by adenosine diphosphate and for the observed changes in platelet surface charge. There is evidence that in general electrostatic interactions are important in the contact relationships between the blood cellular elements and other surfaces either natural or foreign.

Explore related subjects

Adenosine DiphosphateAnimalsBlood ProteinsBlood VesselsCations, DivalentElectrochemistryEndotheliumHumansHydrogen-Ion ConcentrationMicePlatelet AdhesivenessPlatelet AggregationSurface PropertiesJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

G V Seaman. 1983. Plasma protein interactions at biological interfaces.. https://pubmed.ncbi.nlm.nih.gov/6579719/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.

PURPOSE: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs). METHODS: Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants. RESULTS: DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2. CONCLUSION: We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.

Adenosine Diphosphate↗
PubMed2007

A mobile tryptophan is the intrinsic charge transfer donor in a flavoenzyme essential for nikkomycin antibiotic biosynthesis.

The flavoenzyme nikD is required for the biosynthesis of nikkomycin antibiotics. NikD exhibits an unusual long wavelength absorption band attributed to a charge transfer complex of FAD with an unknown charge transfer donor. NikD crystals contain an endogenous active site ligand. At least four different compounds are detected in nikD extracts, including variable amounts of two ADP derivatives that bind to the enzyme's dinucleotide binding motif in competition with FAD, picolinate (0.07 mol/mol of nikD) and an unknown picolinate-like compound. Picolinate, the product of the physiological catalytic reaction, matches the properties deduced for the active site ligand in nikD crystals. The charge transfer band is eliminated upon mixing nikD with excess picolinate but not by a reversible unfolding procedure that removes the picolinate-like compound, ruling out both compounds as the intrinsic charge transfer donor. Mutation of Trp355 to Phe eliminates the charge transfer band, accompanied by a 30-fold decrease in substrate binding affinity. The results provide definitive evidence for Trp355 as the intrinsic charge transfer donor. The indole ring of Trp355 is coplanar with or perpendicular to the flavin ring in "open" or "closed" crystalline forms of nikD, respectively. Importantly, a coplanar configuration is required for charge transfer interaction. Absorption in the long wavelength region therefore constitutes a valuable probe for monitoring conformational changes in solution that are likely to be important in nikD catalysis.

Adenosine Diphosphate↗
PubMed2007

Bioinformatic discovery of novel bioactive peptides.

Short synthetic oligopeptides based on regions of human proteins that encompass functional motifs are versatile reagents for understanding protein signaling and interactions. They can either mimic or inhibit the parent protein's activity and have been used in drug development. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides, often without knowledge of the signaling pathways targeted. Our objective was to determine whether rational bioinformatic design of oligopeptides specifically targeted to potentially signaling-rich juxtamembrane regions could identify modulators of human platelet function. High-throughput in vitro platelet function assays of palmitylated cell-permeable oligopeptides corresponding to these regions identified many agonists and antagonists of platelet function. Many bioactive peptides were from adhesion molecules, including a specific CD226-derived inhibitor of inside-out platelet signaling. Systematic screens of this nature are highly efficient tools for discovering short signaling motifs in molecular signaling pathways.

Adenosine Diphosphate↗