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J Lipid Res. 2013 Oct;54(10):2763-74. doi: 10.1194/jlr.M039545. Epub 2013 Jul 23.

New horizons for lipoprotein receptors: communication by β-propellers.

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Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark; and.


The lipoprotein receptor (LR) family constitutes a large group of structurally closely related receptors with broad ligand-binding specificity. Traditionally, ligand binding to LRs has been anticipated to involve merely the complement type repeat (CR)-domains omnipresent in the family. Recently, this dogma has transformed with the observation that β-propellers of some LRs actively engage in complex formation too. Based on an in-depth decomposition of current structures and sequences, we suggest that exploitation of the β-propellers as binding targets depends on receptor subgroups. In particular, we highlight the shutter mechanism of β-propellers as a general recognition motif for NxI-containing ligands, and we present indications that the generalized β-propeller-induced ligand release mechanism is not applicable for the larger LRs. For the giant LR members, we present evidence that their β-propellers may also actively engage in ligand binding. We therefore advocate for an increased focus on solving the structure-function relationship of this group of important biological receptors.


Tyr-Trp-Thr-Asp β-propeller; endocytosis; internalisation; ligand recognition motif; ligand release; structure

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