Lecture 8 Flashcards
Where is calcium concentration highest
Lowest
Outside the cell
Inside the cell (has resting (lower) and active phase (higher) )
What is calcium used as
A secondary messenger that triggers event in eukaryotic cells
What are the key things in moving calcium
PMCA (Ca2+ atpase/ ca2+ pump)
VGCC (voltage gated calcium channel)
RYR/IP3R
CLSQ (calcium sequestering)
SERCA
What is apo- CAM
Calmodulin but ca2+ Unbound form
Usually mg bound but look like apo so it’s called apo
What is serca
An atpase membrane protein in the SR/ER membrane
It pumps ca2+ into the SR/ER
What is Calsequestrin
In the SR/ER lumen
It binds a lot of ca2+ as storage in the SR/ER lumen
What is PMCA
a calcium pump in the plasma membrane
It pumps out excess ca2+ from the cell
What does calcium calmodulin do to PMCA and VGCC
Binds to their calcium binding domains to
Activate PMCA (to get ca out of cell)
Close VGCC (to make ca not get taken into cell, feedback inhibition)
VGCC is a
Heteropentamer
It’s c term inside the cell
VGCC and other ion channels are a target for
Calcium channel blocker drugs
To keep ca2+ out
How does ca cam inhibit VGCC
Thought feedback inhibition
Binds to the c term cytoplasmic part of the vgcc alpha1 subunit
This binding closes the VGCC channel
What is the inhibition of VGCC called
Calcium dependent inactivation (CDI)
Because calcium binds to cam then cam shuts off the channel
What is an isoform
Spliceoform
Diff genes
Same gene but spliced diff
How does cam bind to caV1.1 (a skeletal muscle isoform of VGCC)
The caV1.1 has a pore that allows ca2+ into the cell
can binds and pulls the two domains of the pore together
Fast inactivation
Binding of ca2+ to cam is
Sequenctial
What type of protein is calmodulin
And EF hand protein
Had 400 diff target sites (it can do many things)
What else can ca cam activate
myosin light chain kinase (MLCK)
Bind to the loop in the MLCK c term domain and pulls it off to activate it
Involved in muscle contraction
What are EF hand proteins
A protein with a EF hand motif (helix loop helix)
Connected by a small beta sheet
binds Ca in the palm of the hand
How many EF hand motifs does ca calmodulin have
4
They are organized into the n lobe and the c lobe
Will position 6 of the EF hand motif ever not be glycine
What’s always in position 1
No
Always asp in position 1
How does the EF hand bind ca
In apo state (no ca bound) the hand is closed
When ca, the hand opens and make a pocket that the substrate (whatever it’s activating) can sit in
Once ca bind to to what am happens to the structure
In apo it’s disordered, but when ca binds The structures alpha helix forms then it can bind other proteins
What do the methionine residues in cam do
How many does it have
Make cam sticky so that ca2+ binds (since hydrophobic want to be sheilded)
9 in total (4 in each lobe)
Cam is a good
Secondary messenger of proteins because it can bind in many ways
