1XFE

Solution structure of the LA7-EGFA pair from the LDL receptor

Summary for 1XFE

• Entry DOI: 10.2210/pdb1xfe/pdb
• Descriptor: Low-density lipoprotein receptor, CALCIUM ION (2 entities in total)
• Functional Keywords: ligand-binding repeat, egf-like repeat, lipid transport, endocytosis-exocytosis complex, endocytosis/exocytosis
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01130
• Total number of polymer chains: 1
• Total formula weight: 9295.57

Authors

Beglova, N.,Jeon, H.,Fisher, C.,Blacklow, S.C. (deposition date: 2004-09-14, release date: 2004-11-02, Last modification date: 2024-10-30)

Primary citation

Beglova, N.,Jeon, H.,Fisher, C.,Blacklow, S.C.
Cooperation between Fixed and Low pH-Inducible Interfaces Controls Lipoprotein Release by the LDL Receptor
Mol.Cell, 16:281-292, 2004

PubMed Abstract: Low-density lipoprotein (LDL) receptors bind lipoprotein particles at the cell surface and release them in the low pH environment of the endosome. The published structure of the receptor determined at endosomal pH reveals an interdomain interface between its beta propeller and its fourth and fifth ligand binding (LA) repeats, suggesting that the receptor adopts a closed conformation at low pH to release LDL. Here, we combine lipoprotein binding and release assays with NMR spectroscopy to examine structural features of the receptor promoting release of LDL at low pH. These studies lead to a model in which the receptor uses a pH-invariant scaffold as an anchor to restrict conformational search space, combining it with flexible linkers between ligand binding repeats to interconvert between open and closed conformations. This finely tuned balance between interdomain rigidity and flexibility is likely to represent a shared structural feature in proteins of the LDL receptor family.

PubMed: 15494314
DOI: 10.1016/j.molcel.2004.09.038

Experimental method

SOLUTION NMR