The structure-function relationship of a signaling-competent, dimeric Reelin fragment. Academic Article uri icon

Overview

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.

publication date

  • June 4, 2021

Research

keywords

  • Reelin Protein

Identity

Scopus Document Identifier

  • 85116406816

Digital Object Identifier (DOI)

  • 10.1016/j.str.2021.05.012

PubMed ID

  • 34089653

Additional Document Info

volume

  • 29

issue

  • 10