Proteopathic diseases and amelogensis imperfecta Flashcards
what is the definition of proteopathies
class of diseases where proteins structure becomes abnormal and disrupts the function of cells, tissues, and organs of the body
what usually happens to the protein structure
fail to fold into their normal configuration
why is the misfiled state dangerous
the proteins can become toxic and lose their normal function
what can lead to misfoldings of proteins
mutations and this can also lead to abnormal aggregation
what is an example of proteopathy
alzheimers disease- which occurs due to an accumulation of misfiled protein in the brain which forms plaques
what is the major aggregating protein in some forms of amelogenesis imperfecta
amelogenin
what are the stages of protein synthesis
- begins when a gene on DNA produces mRNA
- the mRNA leaves via nuclear pore and attaches to a ribosome in the cytoplasm or on RER
- when proteins are produced via transcription and translation they are released into the cytoplasm
- protein is threaded into the tubes of the ER where it starts to fold into 3D shape
- the proteins are modified here and bud off in a transport vesicle
- the transport vesicle moves the protein to the golgi apparatus on the receiving face of the golgi
- in the cisternae of the golgi modification and packing occurs and moves towards the shipping face
- on the shipping face side - one type can become a lysosome and contain digestive enzymes
- transport of the vesicle and fuses with the membrane and exocytosis of the protein occurs
what are the types of vesicles that can be produced
transport vesicle
membrane renewal vesicle-
secreting vesicle- secrete products by fusing with the membrane and removing products by exocytosis
what do membrane renewal vesicles do
add new lipids and proteins to reform the membrane
what do secreting vesicles do
secrete products by fusing with the membrane and removing products by exocytosis
what issues can happen in the ER
misfolded proteins can accumulate in the space and stall this causes stress in the cell and can cause apoptosis
how is a protein identified as a secretory protein
the protein has sequence a N terminus which is called the signal peptide
what is the signal peptide
it is a short peptide located on the N terminus of the amino acid( at the beginning) which identifies the protein is secretory
what are the stages of translocation of proteins to the ER of CO translational translocation
- the protein has sequence a N terminus which is called the signal peptide- this is identified
- the peptide is inserted into a translocation channel in the ER membrane and the process continues and the protein is translocated into the ER
what are the stages of POST translational translocation
- protein translated first completely in cytoplasm
2. because of the signal recognition sequence gets translocated into the ER
what is protein folding directed by
chaperones
what is an example of a chaperone
BIP
what are chaperones
proteins that accompany proteins to other areas and asssit with correct folding
what reaction is protein folding
a dynamic process which takes time
what type of structures form first in protein folding
local secondary structures such as a helix or B pleated sheet
what forms after local secondary structures
longer range interactions
what problems can you encounter if you have a point mutation
will change the primary structure—-> then the secondary and result in the misfolded protein—-> this can result in the protein aggregating and fibres accumulating in the ER—-> leading to ER stress and then disease eg Alzheimers
what can happen in the ER when a protein is misfolded
protein aggregation,
inclusion bodies and fibres accumulate in the ER
what can happen if we have a protein with a neutral charge that undergoes a point mutation and becomes charged
the protein will have a charge and form interactions leading to irreversible protein damage by protein misfolding
