Week 8 Flashcards
1
Q
Why don’t humans get T. brucei brucei?
A
- have a trypanosome lytic factor (TLF) in blood serum
- it is a High density lipoprotein (HDL)
cholesterol molecule - the TLF contains HPR, which binds to the parasite receptor and it then takes up the entire molecule
- as parasite breaks down the cholesterol molecule and releases APOL1 (lytic factor)
- APOL1 forms pore in plasma membrane of the parasite and kills it
2
Q
How do we get trypanosomiasis?
A
- they have evolved to evade the trypanosome lytic factor (TLF)
- they modified their receptors
- resistant version actively express the SRA version of the surface coat
- it does not interact with HPR and it does not bring in APOL1
3
Q
How have baboons evolved to surpass the SRA coat modification of trypanosomes?
A
- have mutations near their C-terminus
- allows APOL1 to bind to SRA, does not need HPR
4
Q
G1/G2 mutants
A
- human variants of APOL1 that makes them more resistant to human trypanozomes
- results in kidney disease if homozygotes
5
Q
How does T.brucei persist?
A
- Antigenic variation – the parasite is changing its surface coat each spike
6
Q
Trypanosome surface
A
- In the human host, the surface is covered in variant surface glycoproteins (VSGs)
- As the host raises a reaction, a small number of individuals with a different coat expand
- variable region of the VSG is the only part the immune system can touch
7
Q
3 functions of the variable region of VSG
A
- Shields
- shields parasite, it is the only thing host immune system can interact with - Switches
- changes versions (coats) - Cleans
- it is sticky so host proteins bind to it
- get recycled to get rid of them
- keep making copies of the same VSG
8
Q
What are the 2 problems raised by the switching mechanism of the variable region of the VSG?
A
- How to express only one VSG at a time
- How to switch between expressed VSGs
9
Q
Expression Site (ES)
A
- only ~20 ESs in the genome (even though there are hundreds of VSGs)
- found in telomeres of larger chromosomes
- physical site where this special
transcription occurs, and only one ES can sit in that physical space at a time - allows for only one VSG to be expressed
10
Q
Gene Conversion switching (VSG)
A
- silent VSG gene is copied and recombined into the active VSG Expression Site (ES)
- original active VSG gene is replaced, and the newly inserted VSG gene is expressed
- donor VSG gene remains intact in its original location, but a duplicate is now in the active site
11
Q
Transcriptional switching (VSG)
A
parasite activates a different VSG expression site (ES), which contains a different VSG gene
12
Q
kDNA (kinetoplast DNA)
A
- makes loops
- non-linear circles of DNA
Two types: - maxicircle
- minicircle: contains gRNA (guide RNAs)
- the DNA does not code for proteins but it does code for the RNA that codes for the right proteins
13
Q
RNA editing in kDNA
A
- after being transcribed, it undergoes RNA editing
- ## it is the addition (insertion editing) or removal (deletion editing) of uracils that makes the mRNA longer and makes it able to encode proteins
14
Q
RNA editing directed by guide RNAs
A
- the gRNA contains an anchor at it’s 5’ end that is complementary to the gene it needs to edit
- it binds to the 3’ end of the mRNA
- the information section of the gRNA gives the editing complex info on where to add and subtract
- once it reaches the U tail region of the gRNA, it falls of
- Editing of a downstream region is required for binding of the subsequent gRNA’s anchor region
15
Q
Kinetoplast drugs
A
- Many are known to build up in the
mitochondrion (good) - In T. brucei the kinetoplast is generally considered essential (good)
- there are natural tryps without
kinetoplasts (bad)
