Domain structure and intramolecular regulation of dynamin GTPase

Amy B. Muhlberg, Dale E. Warnock, Sandra L. Schmid

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

Dynamin is a 100 kDa GTPase required for receptor-mediated endocytosis, functioning as the key regulator of the late stages of clathrin-coated vesicle budding. It is specifically targeted to clathrin-coated pits where it self-assembles into 'collars' required for detachment of coated vesicles from the plasma membrane. Self-assembly stimulates dynamin GTPase activity. Thus, dynamin-dynamin interactions are critical in regulating its cellular function. We show by crosslinking and analytical ultracentrifugation that dynamin is a tetramer. Using limited proteolysis, we have defined structural domains of dynamin and evaluated the domain interactions and requirements for self-assembly and GTP binding and hydrolysis. We show that dynamin's C-terminal proline- and arginine-rich domain (PRD) and dynamin's pleckstrin homology (PH) domain are, respectively, positive and negative regulators of self-assembly and GTP hydrolysis. Importantly, we have discovered that the α-helical domain interposed between the PH domain and the PRD interacts with the N-terminal GTPase domain to stimulate GTP hydrolysis. We term this region the GTPase effector domain (GED) of dynamin.

Original languageEnglish (US)
Pages (from-to)6676-6683
Number of pages8
JournalEMBO Journal
Volume16
Issue number22
StatePublished - Dec 8 1997

Keywords

  • Dynamin
  • Endocytosis
  • GTPase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Muhlberg, A. B., Warnock, D. E., & Schmid, S. L. (1997). Domain structure and intramolecular regulation of dynamin GTPase. EMBO Journal, 16(22), 6676-6683.