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PMID: 16456543 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion.

The EMBO journal ·Vol. 25 ·No. 4 ·2006-02-22 ·Pages 701-12

Aricescu AR, Hon WC, Siebold C, Lu W, van der Merwe PA, Jones EY

Abstract

Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a systematic investigation of the cell-adhesive properties of the extracellular region of RPTPmu, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N-terminal MAM (meprin/A5/mu) and Ig domains was determined at 2.7 A resolution; this assigns the MAM fold to the jelly-roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites.

MeSH Terms
Catalytic Domain/physiology Cell Adhesion/physiology Cell Line Crystallography, X-Ray Fibronectins/chemistry Humans Mutagenesis, Site-Directed Protein Structure, Tertiary/physiology Protein Tyrosine Phosphatases/chemistry,genetics,metabolism Receptor-Like Protein Tyrosine Phosphatases, Class 2 Structural Homology, Protein
Chemicals
Fibronectins fibronectin type III like peptide, human PTPRM protein, human Protein Tyrosine Phosphatases Receptor-Like Protein Tyrosine Phosphatases, Class 2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Aricescu Alexandru Radu
Division of Structural Biology, Henry Wellcome Building of Genomic Medicine, University of Oxford, Oxford, UK.
Hon Wai-Ching
Siebold Christian
Lu Weixian
van der Merwe Philip Anton
Jones Edith Yvonne
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600974
Published
2006-02-22
Epub
2006-00-02
Pages
701-12
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1383555
Subset
IM
Grants
Medical Research Council · G9722488 · United Kingdom
Medical Research Council · G9900061 · United Kingdom
External Links
PubMed source DOI: 10.1038/sj.emboj.7600974 PMC Full Text View journal details
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