New horizons for lipoprotein receptors: communication by β-propellers

• Main Authors: Olav M. Andersen, Robert Dagil, Birthe B. Kragelund
• Format: Article
• Language: English
• Published: Elsevier 2013-10-01
• Series: Journal of Lipid Research
• Subjects: Tyr-Trp-Thr-Asp β-propeller; ligand recognition motif; endocytosis; internalisation; ligand release; structure
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520353025

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.