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Updated: Nov 3, 2025

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
The structure-function relationship of a signaling-competent, dimeric Reelin fragment
Liam S Turk1, Xuyuan Kuang2, Valentina Dal Pozzo3
1Child Health Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA; School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.
Abstract:
Reelin operates through canonical and non-canonical pathways that mediate several aspects of brain development and function. Reelin's dimeric central fragment (CF), generated through proteolytic cleavage, is required for the lipoprotein-receptor-dependent canonical pathway activation. Here, we analyze the signaling properties of a variety of Reelin fragments and measure the differential binding affinities of monomeric and dimeric CF fragments to lipoprotein receptors to investigate the mode of canonical signal activation. We also present the cryoelectron tomography-solved dimeric structure of Reelin CF and support it using several other biophysical techniques. Our findings suggest that Reelin CF forms a covalent parallel dimer with some degree of flexibility between the two protein chains. As a result of this conformation, Reelin binds to lipoprotein receptors in a manner inaccessible to its monomeric form and is capable of stimulating canonical pathway signaling.
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