LDL Receptor
PDB file 1N7D
This file depicts the extracellular domain of the human LDL receptor. Structure solved by G. Rudenko, L. Henry, K. Henderson, K. Ichtchenko, M. S. Brown, J. L. Goldstein & J. Deisenhofer in 2002.
Suggested display options:
Select protein, display as cartoon and
color structure.
Look for the b-propeller
structure.
Select hetero-ligand, display as
ball & stick with color
CPK.
You can ignore the ligands designated KEG, which are phosphotungstate complexes.
Examine the nature of the sugar chains on
this glycoprotein.
Compare to diagram of a typical N-linked oligosaccharide chain above.
Question: To what type of amino acid side chain is
each sugar chain linked?
The LDL apoprotein B100 is bound by a series of cysteine-rich repeats, that are
stabilized by disulfide bridges. Each repeat includes a binding site for calcium.
Select and display all Cys residues as
spacefill, with color
CPK.
Also use the command line to select calcium;
then display as spacefill
with color CPK.
Note the positions of the domains with
disulfide linkages.
Identify acidic residues that serve as ligands to the bound Ca++ ions.
In this sample crystallized at acidic pH (as in an endosome) two of the
cysteine-rich repeats, designated R4 (127-163)
and R5 (176-210) make contact with the
b-propeller. It is postulated that this interaction,
favored at acidic pH, causes the receptor to release bound LDL.
Select segments 127-163,
176-210, change their display and
note their location.
Find the two His residues in the b-propeller
and one pointing at the b-propeller from R5 that are
thought to form salt bridges that would titrate as pH changes from the
extracellular space to the more acidic endosomal lumen.
(The pKa of the His side-chain is such that it would have a + charge
within the endosome.)
At the more neutral pH of the extracellular space, R4 & R5 domains have a lowered affinity
for the b propeller domain.
Question: What
might be the conformation of the string of cysteine-rich domains
if not bound by the b-propeller?
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