scholarly journals Preferential antagonism of the interactions of the integrin αIIbβ3 with immobilized glycoprotein ligands by snake-venom RGD (Arg-Gly-Asp) proteins. Evidence supporting a functional role for the amino acid residues flanking the tripeptide RGD in determining the inhibitory properties of snake-venom RGD proteins

1994 ◽  
Vol 304 (3) ◽  
pp. 929-936 ◽  
Author(s):  
X Lu ◽  
J A Williams ◽  
J J Deadman ◽  
G P Salmon ◽  
V V Kakkar ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Snake Venom ◽  
Cyclic Peptides ◽  
Platelet Adhesion ◽  
Sequence Similarity ◽  
Amino Acid Sequence Similarity ◽  
Adhesion Assay ◽  
Immobilized Ligands ◽  
Venom Proteins

The inhibitory properties of a panel of snake-venom-derived RGD (Arg-Gly-Asp) proteins, including the disintegrins kistrin, elegantin and albolabrin, and the neurotoxin homologue dendroaspin, were investigated in a platelet-adhesion assay using three immobilized ligands of the glycoprotein IIb-IIIa complex (alpha IIb beta 3), namely fibrinogen, fibronectin and von Willebrand factor (vWF). The snake-venom proteins preferentially inhibited the adhesion of ADP-treated platelets to one or more of the immobilized ligands. Kistrin and dendroaspin exhibited similar inhibitory characteristics, abrogating platelet adhesion to fibrinogen and vWF at nanomolar concentrations, but poorly inhibiting adhesion to fibronectin. Kistrin and dendroaspin share little overall amino-acid-sequence identity, but a considerable level of sequence similarity exists around the RGD tripeptide. Synthetic cyclic peptides corresponding to these regions of kistrin and dendroaspin inhibited platelet adhesion to both fibrinogen and fibronectin with approximately equal potency, but were 100-fold weaker antagonists of the interactions of the alpha IIb beta 3 complex with fibrinogen than their parent proteins. The disintegrins elegantin and albolabrin, which share approx. 60% overall amino-acid-sequence similarity with kistrin but have different residues around the RGD tripeptide, exhibited different antagonistic preferences. Elegantin inhibited platelet adhesion to immobilized vWF and fibronectin, but was significantly less effective at disrupting adhesion to fibrinogen. Albolabrin selectively inhibited platelet adhesion to immobilized vWF and was less effective with fibrinogen and fibronectin as adhesive ligands. In contrast with the behaviour of these venom proteins, the adhesion of ADP-treated platelets to immobilized fibrinogen, fibronectin and vWF was inhibited non-selectively by a range of monoclonal antibodies with specificity for the alpha IIb beta 3 complex. These observations, therefore, define antagonistic preferences in this panel of venom proteins towards the interactions of the alpha IIb beta 3 complex with three immobilized glycoprotein ligands.

scholarly journals Engineered Resistance Against Papaya ringspot virus in Venezuelan Transgenic Papayas

Plant Disease ◽  
2004 ◽  
Vol 88 (5) ◽  
pp. 516-522 ◽  
Author(s):  
Gustavo Fermin ◽  
Valentina Inglessis ◽  
Cesar Garboza ◽  
Sairo Rangel ◽  
Manuel Dagert ◽  
...  
Keyword(s):  
Amino Acid ◽  
Agrobacterium Tumefaciens ◽  
Coat Protein ◽  
Amino Acid Sequence ◽  
Sequence Similarity ◽  
Ringspot Virus ◽  
Amino Acid Sequence Similarity ◽  
Papaya Ringspot Virus ◽  
Local Varieties ◽  
Cp Gene

Local varieties of papaya grown in the Andean foothills of Mérida, Venezuela, were transformed independently with the coat protein (CP) gene from two different geographical Papaya ringspot virus (PRSV) isolates, designated VE and LA, via Agrobacterium tumefaciens. The CP genes of both PRSV isolates show 92 and 96% nucleotide and amino acid sequence similarity, respectively. Four PRSV-resistant R0 plants were intercrossed or selfed, and the progenies were tested for resistance against the homologous isolates VE and LA, and the heterologous isolates HA (Hawaii) and TH (Thailand) in greenhouse conditions. Resistance was affected by sequence similarity between the transgenes and the challenge viruses: resistance values were higher for plants challenged with the homologous isolates (92 to 100% similarity) than with the Hawaiian (94% similarity) and, lastly, Thailand isolates (88 to 89% similarity). Our results show that PRSV CP gene effectively protects local varieties of papaya against homologous and heterologous isolates of PRSV.

scholarly journals High-Efficiency Utilization of the Bovine Integrin αvβ3 as a Receptor for Foot-and-Mouth Disease Virus Is Dependent on the Bovine β3Subunit

2000 ◽  
Vol 74 (16) ◽  
pp. 7298-7306 ◽  
Author(s):  
Sherry Neff ◽  
Peter W. Mason ◽  
Barry Baxt
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Disease Virus ◽  
Sequence Similarity ◽  
Foot And Mouth Disease ◽  
Viral Proteins ◽  
Mouth Disease ◽  
Amino Acid Sequence Similarity ◽  
Mouth Disease Virus ◽  
Human Integrin

ABSTRACT We have previously reported that Foot-and-mouth disease virus (FMDV), which is virulent for cattle and swine, can utilize the integrin αvβ3 as a receptor on cultured cells. Since those studies were performed with the human integrin, we have molecularly cloned the bovine homolog of the integrin αvβ3 and have compared the two receptors for utilization by FMDV. Both the αv and β3subunits of the bovine integrin have high degrees of amino acid sequence similarity to their corresponding human subunits in the ectodomains (96%) and essentially identical transmembrane and cytoplasmic domains. Within the putative ligand-binding domains, the bovine and human αv subunits have a 98.8% amino acid sequence similarity while there is only a 93% similarity between the β3 subunits of these two species. COS cell cultures, which are not susceptible to FMDV infection, become susceptible if cotransfected with αv and β3 subunit cDNAs from a bovine or human source. Cultures cotransfected with the bovine αvβ3 subunit cDNAs and infected with FMDV synthesize greater amounts of viral proteins than do infected cultures cotransfected with the human integrin subunits. Cells cotransfected with a bovine αv subunit and a human β3subunit synthesize viral proteins at levels equivalent to those in cells expressing both human subunits. However, cells cotransfected with the human αv and the bovine β3 subunits synthesize amounts of viral proteins equivalent to those in cells expressing both bovine subunits, indicating that the bovine β3 subunit is responsible for the increased effectiveness of this receptor. By engineering chimeric bovine-human β3subunits, we have shown that this increase in receptor efficiency is due to sequences encoding the C-terminal one-third of the subunit ectodomain, which contains a highly structured cysteine-rich repeat region. We postulate that amino acid sequence differences within this region may be responsible for structural differences between the human and bovine β3 subunit, leading to more efficient utilization of the bovine receptor by this bovine pathogen.

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