BIOC 212 Lecture Notes - Lecture 31: Collagen, White Blood Cell, Cytoskeleton
29 May 2018
School
Department
Course
Professor
Cell Junctions & Cell Adhesion XI
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Disintegrins
• Large group of snake (viper) venom proteins containing a number of cysteine
residues and RGD sequence
o Small peptides isolated from snakes
o Australia has most poisonous snake
• More than 40 different ones identified
• Small protein, 40-100 aa long (high homology)
o Cysteine-rich with RGD motif
o Can competitively displace the normal binding ligand (i.e. fibronectin)
• Compete with binding on integrin
• Able to displace due to high affinity
• Block functions of some integrins
o Through RDG motifs, disintegrins bind to integrins and inhibit their function
o Work by countering blood clotting steps, inhibiting clumping of platelets
• i.e. inhibit integrin-fibrin interaction
• Act as competitive inhibitor for integrin-fibrin interaction, and block coagulation
o Anti-coagulation agents (aIIbb3)
• Coagulation is blood clot formation in wounding situation; prevent further
bleeding
• Embolism: internal blood clot getting caught somewhere --need to
dissolve it and avoid internal blood clotting
o Angiogenesis inhibitors (anti-cancer drugs, avb3)
• Block angiogenesis; can be useful in development of anti-cancer drugs;
inhibiting formation of blood vessels into mass to vascularize cancer
• Cancer cell growing somewhere in body, starting from single cells,
needs vascularization when 1mm big
• Integrin is extremely important in blood vessel formation
Integrin Activation --Cell Aggregation
• Integrins frequently need activation
o Example platelet aggregation (blood clotting)
• Alpha llb beta 3 is present on the surface of platelets, but is unable to bind the
blood protein fibrinogen & other proteins
o aIIb subunit in combination with beta 3 subunit important for blood clot
formation
o Normally, this integrin is inactive --> if were active all the same would always
get blood clotting
• Need system that only triggers blood clot formation when there is a
wound
