Solution structure of a syndecan-4 cytoplasmic domain and its interaction with phosphatidylinositol 4,5-bisphosphate

Donghan Lee, Eok Soo Oh, Anne Woods, John R. Couchman, Weon Tae Lee

Research output: Contribution to journalArticle

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Abstract

Syndecan-4, a transmembrane heparan sulfate proteoglycan, is a coreceptor with integrins in cell adhesion. It has been suggested to form a ternary signaling complex with protein kinase Ca and phosphatidylinositol 4,5-bisphosphate (PIP2). Syndecans each have a unique, central, and variable (V) region in their cytoplasmic domains, and that of syndecan-4 is critical to its interaction with protein kinase C and PIP2. Two oligopeptides corresponding to the variable region (4V) and whole domain (4L) of syndecan- 4 cytoplasmic domain were synthesized for nuclear magnetic resonance (NMR) studies. Data from NMR and circular dichroism indicate that the cytoplasmic domain undergoes a conformational transition and forms a symmetric dimer in the presence of phospholipid activator PIP2. The solution conformations of both free and PIP2-complexed 4V have been determined by two-dimensional NMR spectroscopy and dynamical simulated annealing calculations. The 4V peptide in the presence of PIP2 formed a compact dimer with two twisted strands packed parallel to each other and the exposed surface of the dimer consisted of highly charged and polar residues. The overall three-dimensional structure in solution exhibits a twisted clamp shape having a cavity in the center of dimeric interface. In addition, it has been observed that the syndecan-4V strongly interacts not only with fatty acyl groups but also the anionic head group of PIP2. These findings reveal that PIP2 promotes oligomerization of syndecan-4 cytoplasmic domain for transmembrane signaling and cell-matrix adhesion.

Original languageEnglish
Pages (from-to)13022-13029
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number21
DOIs
Publication statusPublished - 1998 May 22

Fingerprint

Syndecan-4
Phosphatidylinositols
Syndecans
Dimers
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Cell-Matrix Junctions
Heparan Sulfate Proteoglycans
Oligopeptides
Oligomerization
Cell adhesion
Clamping devices
Circular Dichroism
Simulated annealing
Cell Adhesion
Integrins
Protein Kinases
Protein Kinase C
Nuclear magnetic resonance spectroscopy
Conformations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Donghan ; Oh, Eok Soo ; Woods, Anne ; Couchman, John R. ; Lee, Weon Tae. / Solution structure of a syndecan-4 cytoplasmic domain and its interaction with phosphatidylinositol 4,5-bisphosphate. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 21. pp. 13022-13029.
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Solution structure of a syndecan-4 cytoplasmic domain and its interaction with phosphatidylinositol 4,5-bisphosphate. / Lee, Donghan; Oh, Eok Soo; Woods, Anne; Couchman, John R.; Lee, Weon Tae.

In: Journal of Biological Chemistry, Vol. 273, No. 21, 22.05.1998, p. 13022-13029.

Research output: Contribution to journalArticle

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