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Structure of the Wnt signaling enhancer LYPD6 and its interactions with the Wnt co-receptor LRP6

DOI: 10.1002/1873-3468.13212 DOI Help

Authors: Yuguang Zhao (Wellcome Centre for Human Genetics, University of Oxford) , Jingshan Ren (Wellcome Centre for Human Genetics, University of Oxford) , Weixian Lu (Wellcome Centre for Human Genetics, University of Oxford) , Karl Harlos (Wellcome Centre for Human Genetics, University of Oxford) , E. Yvonne Jones (Wellcome Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters

State: Published (Approved)
Published: August 2018
Diamond Proposal Number(s): 8423

Abstract: LYPD6 is a Wnt signaling enhancer that promotes phosphorylation of the Wnt co‐receptor LRP6 (low‐density lipoprotein receptor‐related protein 6). It also binds the nicotinic acetylcholine receptor (nAChR). We report here the 1.25 Å resolution structure of the LYPD6 extracellular Ly6/uPAR (LU) domain and map its interaction with LRP6 by mutagenesis and surface plasmon resonance (SPR). The LYPD6LU structure reveals a “tri‐fingered protein domain” fold with the middle fingertip of the bearing a “NxI” motif, a tripeptide motif associated with LRP5/6 binding by Wnt inhibitors. Of the Ly6 protein family members, only LYPD6 has an NxI motif. Since mutations in the LYPD6 NxI motif abolish or severely reduce interaction with LRP6, our results indicate its key role in the interaction of LYPD6 with LRP6.

Journal Keywords: LYPD6; LRP6 binding; NxI motif

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 09/08/2018 10:11

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)