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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