Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function

Chengmin Qian, Qiang Zhang, Xueqi Wang, Lei Zeng, Amjad Farooq, Ming Ming Zhou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The adaptor protein p14 is associated with the cytoplasmic face of late endosomes that is involved in cell-surface receptor endocytosis and it also directly interacts with MP1, a scaffolding protein that binds the MAP kinase ERK1 and its upstream kinase activator MEK1. The interaction of p14 with MP1 recruits the latter to late endosomes and the endosomal localization of p14/MP1-MEK1-ERK1 scaffolding complex is required for signaling via ERK MAP kinase in an efficient and specific manner upon receptor stimulation. Here, we report the three-dimensional solution structure of the adaptor protein p14. The structure reveals a profilin-like fold with a central five-stranded β-sheet sandwiched between α-helices. Unlike profilin, however, p14 exhibits weak interaction with selective phosphoinositides but no affinity towards proline-rich sequences. Structural comparison between profilin and p14 reveals the molecular basis for the differences in these functions. We further mapped the MP1 binding sites on p14 by NMR, and discuss the implications of these important findings on the possible function of p14.

Original languageEnglish
Pages (from-to)309-321
Number of pages13
JournalJournal of Molecular Biology
Volume347
Issue number2
DOIs
StatePublished - Mar 25 2005

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Profilins
Endosomes
Proteins
Mitogen-Activated Protein Kinase 3
Extracellular Signal-Regulated MAP Kinases
Cell Surface Receptors
Phosphatidylinositols
Endocytosis
Proline
Phosphotransferases
Binding Sites

Keywords

  • MAP kinase
  • MP1
  • NMR
  • p14
  • Three-dimensional structure

ASJC Scopus subject areas

  • Virology

Cite this

Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function. / Qian, Chengmin; Zhang, Qiang; Wang, Xueqi; Zeng, Lei; Farooq, Amjad; Zhou, Ming Ming.

In: Journal of Molecular Biology, Vol. 347, No. 2, 25.03.2005, p. 309-321.

Research output: Contribution to journalArticle

Qian, Chengmin ; Zhang, Qiang ; Wang, Xueqi ; Zeng, Lei ; Farooq, Amjad ; Zhou, Ming Ming. / Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function. In: Journal of Molecular Biology. 2005 ; Vol. 347, No. 2. pp. 309-321.
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