Disease relevance of FGG

• Expression and analysis of a split premature termination codon in FGG responsible for congenital afibrinogenemia: escape from RNA surveillance mechanisms in transfected cells [1].
• No fibrin degradation product was observed in plasma samples, however, high amounts of fibrinogen gamma-chain dimer crosslinked by transglutaminase were detected in plasma from tumor patients, but not in plasma from controls and patients suffering acute infections and/or inflammations [2].
• In conclusion, fibrinogen FGG and FGA gene haplotypes are not associated with coronary events, coronary atherosclerosis or extracoronary atherosclerosis [3].
• The in vitro kinetic parameters of PRT and FGGP (where FGGP is the single polypeptide form of the HIV-1 protease with 2 glycine residues connecting the two subunits) for three peptide substrates are similar [4].
• Clumping factor A (ClfA) is a surface protein of Staphylococcus aureus bacteria known for its ability to bind the C-terminus of plasma fibrinogen gamma chain, which participates in mediating fibrinogen-platelet interaction and fibrin cross-linking, resulting in thrombus formation [5].

High impact information on FGG

• Thymus-dependent protein antigens such as fowl gamma globulin (FGG) and dinitrophenylated-human gamma globulin (DNP-HGG), readily induced tolerance of the B cell in the absence of T cells even when these antigens were not deaggregated [6].
• In the presence of XIIIa, the Dusart fibrinogen gamma chain cross-linking rate was about twice that of normal, but was normalized in proteolytic fibrinogen derivatives lacking the Aalpha chain abnormality, as was reduced plasminogen binding [7].
• Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding [8].
• The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1 [9].
• We have constructed synthetic peptides modeled on the sequences of (i) Arg-Gly-Asp, present in fibrinogen, fibronectin, and von Willebrand factor, and of (ii) the fibrinogen gamma chain (gamma 400-411) His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val [10].

Biological context of FGG

• The disease is caused by mutations in 1 of the 3 fibrinogen genes FGG, FGA, and FGB, clustered on the long arm of human chromosome 4 [1].
• Expression studies in COS-7 cells demonstrated that the Arg134Xaa codon, which is encoded by adjacent exons (TG-intron 4-A) affected neither mRNA splicing nor stability, but led to the production of an unstable, severely truncated fibrinogen gamma chain that is not incorporated into a functional fibrinogen hexamer [1].
• The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI [11].
• Sixty controls were selected according to FGG 9340T > C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method [11].
• Supplementing data suggest that FGG is distal to MNSs on the long arm of chromosome 4 [12].

Anatomical context of FGG

• This is suggestive of different mechanisms regulating human fibrinogen gamma-chain gene expression in hepatocytes v megakaryocytes that may operate in a tissue-specific manner at the level of 3' RNA processing events [13].
• Fibrinogen gamma-chain mRNA was detected in granulosa cells by polymerase chain reaction analysis, confirming fibrinogen gene expression by these cells [14].
• The peptide analogs of human fibrinogen gamma chain sequence 400-411 possess high selectivity for platelet GPIIb-IIIa because they do not cause detachment of endothelial cells [15].
• This is the first in an adult male and the second published case with a discernible hepatic fibrinogen endoplasmic reticulum storage disease due to an FGG Arg375Trp (fibrinogen Aguadilla) mutation [16].
• This structural difference from hepatic fibrinogen probably results from differences in the processing and/or regulation of the fibrinogen gamma-chain gene in megakaryocytes [17].

Associations of FGG with chemical compounds

• The modification of FGG chain isoform 1 and FGB chain isoforms 1 and 2 was positively correlated with total plasma cholesterol level [18].
• A peptide corresponding to GPIIb alpha 300-312, a presumptive fibrinogen gamma-chain binding site on the platelet integrin GPIIb/IIIa, inhibits the adhesion of platelets to at least four adhesive ligands [19].
• The fibrinogen gamma chain dodecapeptide inhibits agonist-induced aggregation of rabbit platelets and fibrinogen binding to rabbit glycoprotein IIb-IIIa [20].
• Fibrinogen gamma-chain C-terminal peptide HHLG-GAKQAGDV (gamma 12) and alpha-chain peptide GRGDSP are known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet integrin receptor GPIIb/IIIa [21].
• Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under flow [22].

Other interactions of FGG

• Two regions of the fibrinogen alpha chain that contain an RGD motif, as well as the carboxyl-terminus of the fibrinogen gamma chain, represent potential binding sites for GPIIb-IIIa in the fibrinogen molecule [23].
• Structure-function characterization of the novel ICAM-1 recognition of fibrinogen was carried out by synthetic peptidyl mimicry of the fibrinogen gamma chain [24].
• Paris I dysfibrinogenemia: a point mutation in intron 8 results in insertion of a 15 amino acid sequence in the fibrinogen gamma-chain [25].
• These data suggest that the fibrinogen gamma chain region Gly190-Val202 functions as a minimal recognition sequence for the leukocyte integrin CD11b/CD18 [26].
• Design and evaluation of nonpeptide fibrinogen gamma-chain based GPIIb/IIIa antagonists [27].

Analytical, diagnostic and therapeutic context of FGG

• Reverse phase high-performance liquid chromatography (HPLC) analysis of the lysyl endopeptidase digest of the purified gamma-chains of fibrinogen Baltimore III revealed the presence of a peptide that is not found in the digest of the normal fibrinogen gamma-chain [28].
• Fibrinogen gamma-chain dimer indicating fibrin deposition and plasmin-generated fibrinogen beta-chain fragments were identified in various solid tumor types by amino acid sequencing, mass spectrometry analysis and Western blotting [2].
• At equal surface densities, mAbs that bound biphasically, particularly mAb 1C5-A5/2, were more reactive to urea-denatured than native fibrinogen. mAbs 1C5-A5/2 and 44-3 are specific for gamma 1-78 and 95-265, respectively, suggesting that the fibrinogen gamma-chain may be sensitive to changes in conformation induced by immobilization [29].
• To examine the direct interaction of H12 with rabbit GPIIb-IIIa, we performed affinity chromatography by applying an octylglucoside extract of rabbit platelet proteins onto an affinity matrix containing the fibrinogen gamma chain sequence [20].
• Dissecting clot retraction and platelet aggregation. Clot retraction does not require an intact fibrinogen gamma chain C terminus [30].

References