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Title: Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface

Abstract

Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalian α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40–100-fold in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formationmore » in C. elegans. Our data provide novel insights into how cadherin-dependent cell–cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.« less

Authors:
 [1];  [2];  [3];  [4]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [2]; ORCiD logo [6]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Zoology, Program in Genetics
  2. Seoul National Univ. (Korea, Republic of). Biological Sciences
  3. Univ. of Wisconsin, Madison, WI (United States). Program in Genetics and Program in Cellular and Molecular Biology
  4. Seoul National Univ. (Korea, Republic of). Dept. of Chemistry
  5. Stanford Univ., CA (United States). School of Medicine, Dept. of Structural Biology and Molecular and Cellular Physiology
  6. Univ. of Wisconsin, Madison, WI (United States). Dept. of Zoology, Program in Genetics, and Program in Cellular and Molecular Biology
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1425346
Grant/Contract Number:  
AC02-76SF00515; GM094663; GM114462; GM058038; NRF-2016R1A2B4013488; 2015K2A1A2070030
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 292; Journal Issue: 40; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; adherens junction; α-catenin; β-catenin; crystal structure; morphogenesis; cadherin-catenin complex; phosphoregulation

Citation Formats

Shao, Xiangqiang, Kang, Hyunook, Loveless, Timothy, Lee, Gyu Rie, Seok, Chaok, Weis, William I., Choi, Hee-Jung, and Hardin, Jeff. Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface. United States: N. p., 2017. Web. doi:10.1074/jbc.m117.795567.
Shao, Xiangqiang, Kang, Hyunook, Loveless, Timothy, Lee, Gyu Rie, Seok, Chaok, Weis, William I., Choi, Hee-Jung, & Hardin, Jeff. Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface. United States. doi:10.1074/jbc.m117.795567.
Shao, Xiangqiang, Kang, Hyunook, Loveless, Timothy, Lee, Gyu Rie, Seok, Chaok, Weis, William I., Choi, Hee-Jung, and Hardin, Jeff. Fri . "Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface". United States. doi:10.1074/jbc.m117.795567. https://www.osti.gov/servlets/purl/1425346.
@article{osti_1425346,
title = {Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface},
author = {Shao, Xiangqiang and Kang, Hyunook and Loveless, Timothy and Lee, Gyu Rie and Seok, Chaok and Weis, William I. and Choi, Hee-Jung and Hardin, Jeff},
abstractNote = {Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalian α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40–100-fold in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in C. elegans. Our data provide novel insights into how cadherin-dependent cell–cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.},
doi = {10.1074/jbc.m117.795567},
journal = {Journal of Biological Chemistry},
number = 40,
volume = 292,
place = {United States},
year = {2017},
month = {8}
}

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