I wish all of you a Happy New Year 2014!!!
And take care when you go out tonight…
What’s the problem with Apo E4?:
The following image gives you an overview of the general tertiary structure of Apolipoprotein E3 as determined by x-ray cristallography (without binding any lipid components):
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The corkscrew-like parts of the protein are so called alpha-helices (a common secondary structure of proteins). In these, the amino acid sequence forms a helical configuration of the amino acid chain. There are two ends of the amino acid chain: the N-terminal end (ending with -NH2, on the left side) and the C-terminal end (ending with –COOH, on the right side). At position 112 – in the middle of the green helix – you find the Cysteine residue defining Apo E3. With Cysteine at position 112, the Arginine residue at position 61 (at the lower end of the blue helix) gets buried between alpha-helices. There is no relevant interaction between Arg61 and Glu255.
Now, let’s look at the same image for Apolipoprotein E4 – again this is derived from x-ray crystallography:
As you can see, in Apo E4 the Arginine residue at position 112 (in the green helix) forces the Arginine residue at position 61 (in the blue helix) to move outwards. This in turn facilitates a new, relative strong binding to the glutamate residue at position 255 (a so called salt bridge). As a consequence, you now have a domain interaction between the C-terminal and the N-terminal domain; both domains stick together very tightly. This domain interaction seems to be most relevant for the propensity to develop Alzheimer’s disease in patients who express Apo E4.
How do I determine my Apolipoprotein E genotype?
So how do I know what Apo E alleles I have?
There are basically two major approaches to determine which isoforms are found at your Apo E locus:
We have started to work on some FAQ’s. Check them out! Also, the wordpress version was changed to 3.8. I can’t wait to start reports on the latest research findings…
Happy holidays to all of you!!!!
Blog logo, some more features of wordpress and Apo_e4 twitter account created and uploaded…
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How do you like the new logo?
this site will soon be hosting a blog about Apo E4. Please keep checking back regularly – I need to figure a couple of tech things out before things can get going… you might have noticed that things have changed quite a bit here recently, I’m new to wordpress.
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