Structural features of the low-density lipoprotein receptor facilitating ligand binding and release

2004 ◽  
Vol 32 (5) ◽  
pp. 721-723 ◽  
Author(s):  
N. Beglova ◽  
H. Jeon ◽  
C. Fisher ◽  
S.C. Blacklow
Keyword(s):  
Ligand Binding ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Structural Features ◽  
Low Ph ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Epidermal Growth

The LDLR (low-density lipoprotein receptor) is a modular protein built from several distinct structural units: LA (LDLR type-A), epidermal growth factor-like and β-propeller modules. The low pH X-ray structure of the LDLR revealed long-range intramolecular contacts between the propeller domain and the central LA repeats of the ligand-binding domain, suggesting that the receptor changes its overall shape from extended to closed, in response to pH. Here we discuss how the LDLR uses flexibility and rigidity of linkers between modules to facilitate ligand binding and low-pH ligand release.

scholarly journals Ligand Binding Properties of the Very Low Density Lipoprotein Receptor

1999 ◽  
Vol 274 (13) ◽  
pp. 8973-8980 ◽  
Author(s):  
Peter M. Rettenberger ◽  
Kazuhiro Oka ◽  
Lars Ellgaard ◽  
Helle H. Petersen ◽  
Anni Christensen ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Binding Properties ◽  
Density Lipoprotein Receptor

scholarly journals Low pH-Triggered Beta-Propeller Switch of the Low-Density Lipoprotein Receptor Assists Rhinovirus Infection

2009 ◽  
Vol 83 (21) ◽  
pp. 10922-10930 ◽  
Author(s):  
Tuende Konecsni ◽  
Ursula Berka ◽  
Angela Pickl-Herk ◽  
Gerhard Bilek ◽  
Abdul Ghafoor Khan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Ph ◽  
Release Mechanism ◽  
High Avidity ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

ABSTRACT Minor group human rhinoviruses (HRVs) bind three members of the low-density lipoprotein receptor (LDLR) family: LDLR proper, very-LDLR (VLDLR) and LDLR-related protein (LRP). Whereas ICAM-1, the receptor of major group HRVs actively contributes to viral uncoating, LDLRs are rather considered passive vehicles for cargo delivery to the low-pH environment of endosomes. Since the Tyr-Trp-Thr-Asp β-propeller domain of LDLR has been shown to be involved in the dissociation of bound LDL via intramolecular competition at low pH, we studied whether it also plays a role in HRV infection. Human cell lines deficient in LDLR family proteins are not available. Therefore, we used CHO-ldla7 cells that lack endogenous LDLR. These were stably transfected to express either wild-type (wt) human LDLR or a mutant with a deletion of the β-propeller. When HRV2 was attached to the propeller-negative LDLR, a lower pH was required for conversion to subviral particles than when attached to wt LDLR. This indicates that high-avidity receptor binding maintains the virus in its native conformation. HRV2 internalization directed the mutant LDLR but not wt LDLR to lysosomes, resulting in reduced plasma membrane expression of propeller-negative LDLR. Infection assays using a CHO-adapted HRV2 variant showed a delay in intracellular viral conversion and de novo viral synthesis in cells expressing the truncated LDLR. Our data indicate that the β-propeller attenuates the virus-stabilizing effect of LDLR binding and thereby facilitates RNA release from endosomes, resulting in the enhancement of infection. This is a nice example of a virus exploiting high-avidity multimodule receptor binding with an intrinsic release mechanism.

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