MED 3MSB Lecture Notes - Lecture 3: Lipid Bilayer, Adaptive Immune System, Genitourinary System
Lecture 3
Describe general characteristics + roles that antimicrobial peptides play in immune system
Antimicrobial peptides (AMP)
Definition? Amphipathic peptides, secreted by epithelial cells & phagocytes (found in all living orgs)
Function?
-- Act on memb, -- lyse bacterial cell memb directly
-- Attract inflammatory cells to site of inf
-- Regulate process in adaptive immune system
Characteristics? Small (10-80 aa) +vely charged (cationic)
Location? (in humans) - on epithelial surfaces [mouth, lungs, kidney, intestine, lymphocytes, skin, neutrophil, urogenital tract]
e.g. (humans) – defensins, cathelicidins, histatins
(plants)
How are AMP classified? Based on Structure !!
1. Disulfide-rich
2. Linear a-helical peptides
3. Peptides enriched in specific aa
(Pro,Gly,His,Trp)
• defensin
• structural scaffold
• In plants, insects, mammals (ЍЎθ)
Human -Defensins
▪ Classical
▪ 29-35 aa – 3 disulfide bonds
▪ 6 in humans
Activation ?
Ѝ-Defensins are made ‘pre-prodefensins’
pro-Ѝ-defensins = Inactive
to activate? Proteolytic removal of prodomain
Human Ў-Defensins
▪ Larger (38-42 aa)
▪ Diff cysteine pairing & spacing
▪ 50 in human genome
Activation?
β-Defensins made as pre-prodefensins
shorter prodomains
constitutive/induced expression
Mode of Action in AMPS
Selective inhibition of intracellular targets?
• Bind nucleic acids (buforin II)
• Induce changes in transcriptional profiles (cecropin A)
• Inhibit protein translation (purothionin)
• Interact with mitochondria (histatin-5)
Proposed mechanism of action of cationic AMPs
• Interact with memb &↑their permeability
– positive charges on peptide with anionic lipids of memb
– membrane destabilization thro lipid displacements
– form ion-permeable channels in lipid bilayer
• Induction of hydrolases which degrade cell wall
• Inhibit crucial intracellular targets after internalization of peptide
AMPs Memb target of unicellular organisms
& basis of specificity
•Peptides disrupt the
membrane by orienting
parallel to the surface
of the lipid bilayer
•Forms an extensive
layer or carpet
Hydrophilic = red
find more resources at oneclass.com
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Document Summary
Describe general characteristics + roles that antimicrobial peptides play in immune system. Amphipathic peptides, secreted by epithelial cells & phagocytes (found in all living orgs) - act on memb, -- lyse bacterial cell memb directly. - attract inflammatory cells to site of inf. Location? (in humans) - on epithelial surfaces [mouth, lungs, kidney, intestine, lymphocytes, skin, neutrophil, urogenital tract] e. g. (humans) defensins, cathelicidins, histatins (plants: disulfide-rich. Based on structure : defensin, in plants, insects, mammals ((cid:1037)(cid:1038) ) structural scaffold. Human -defensins: classical, 29-35 aa 3 disulfide bonds, 6 in humans. Activation ? (cid:1037)-defensins are made pre-prodefensins" pro-(cid:1037)-defensins = inactive. Human (cid:1038)-defensins: larger (38-42 aa, diff cysteine pairing & spacing, 50 in human genome. Defensins made as pre-prodefensins shorter prodomains constitutive/induced expression. Selective inhibition of intracellular targets: bind nucleic acids (buforin ii, induce changes in transcriptional profiles (cecropin a, inhibit protein translation (purothionin, interact with mitochondria (histatin-5) Positive charges on peptide with anionic lipids of memb.
