Structural basis of human VANGL-PRICKLE interaction

Abstract Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-lik...

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Main Authors: Yanyi Song, Shuyi Jian, Junlin Teng, Pengli Zheng, Zhe Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55396-3
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author Yanyi Song
Shuyi Jian
Junlin Teng
Pengli Zheng
Zhe Zhang
author_facet Yanyi Song
Shuyi Jian
Junlin Teng
Pengli Zheng
Zhe Zhang
author_sort Yanyi Song
collection DOAJ
description Abstract Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear. Here, we present five cryo-electron microscopy structures of human VANGL1, VANGL2, and their complexes with PK1 at resolutions of 2.2–3.0 Å. Through biochemical and cell imaging experiments, we decipher the molecular details of the VANGL-PK interaction. Furthermore, we reveal that PK1 can target VANGL-containing intracellular vesicles to the peripheral cell membrane. These findings provide a solid foundation to understand the explicit interaction between VANGL and PK while opening new avenues for subsequent studies of the PCP pathway.
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institution Kabale University
issn 2041-1723
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spelling doaj-art-757d02118e5e457bae16a27e505362422025-01-05T12:38:31ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-55396-3Structural basis of human VANGL-PRICKLE interactionYanyi Song0Shuyi Jian1Junlin Teng2Pengli Zheng3Zhe Zhang4State Key Laboratory of Membrane Biology, Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking UniversityMOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityMOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityMOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityState Key Laboratory of Membrane Biology, Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking UniversityAbstract Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear. Here, we present five cryo-electron microscopy structures of human VANGL1, VANGL2, and their complexes with PK1 at resolutions of 2.2–3.0 Å. Through biochemical and cell imaging experiments, we decipher the molecular details of the VANGL-PK interaction. Furthermore, we reveal that PK1 can target VANGL-containing intracellular vesicles to the peripheral cell membrane. These findings provide a solid foundation to understand the explicit interaction between VANGL and PK while opening new avenues for subsequent studies of the PCP pathway.https://doi.org/10.1038/s41467-024-55396-3
spellingShingle Yanyi Song
Shuyi Jian
Junlin Teng
Pengli Zheng
Zhe Zhang
Structural basis of human VANGL-PRICKLE interaction
Nature Communications
title Structural basis of human VANGL-PRICKLE interaction
title_full Structural basis of human VANGL-PRICKLE interaction
title_fullStr Structural basis of human VANGL-PRICKLE interaction
title_full_unstemmed Structural basis of human VANGL-PRICKLE interaction
title_short Structural basis of human VANGL-PRICKLE interaction
title_sort structural basis of human vangl prickle interaction
url https://doi.org/10.1038/s41467-024-55396-3
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AT shuyijian structuralbasisofhumanvanglprickleinteraction
AT junlinteng structuralbasisofhumanvanglprickleinteraction
AT penglizheng structuralbasisofhumanvanglprickleinteraction
AT zhezhang structuralbasisofhumanvanglprickleinteraction