3TFM

Myosin X PH1N-PH2-PH1C tandem

Summary for 3TFM

• Entry DOI: 10.2210/pdb3tfm/pdb
• Descriptor: Myosin X, PHOSPHATE ION (3 entities in total)
• Functional Keywords: split ph domain, motor protein
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 1
• Total formula weight: 26585.54

Authors

Yu, J.,Lu, Q.,Yan, J.,Wei, Z.,Zhang, M. (deposition date: 2011-08-16, release date: 2011-12-07, Last modification date: 2023-11-01)

Primary citation

Lu, Q.,Yu, J.,Yan, J.,Wei, Z.,Zhang, M.
Structural basis of the myosin X PH1N-PH2-PH1C tandem as a specific and acute cellular PI(3,4,5)P3 sensor
MOLECULAR BIOLOGY OF THE CELL, 22:4268-4278, 2011

PubMed Abstract: Myosin X (MyoX) is an unconventional myosin that is known to induce the formation and elongation of filopodia in many cell types. MyoX-induced filopodial induction requires the three PH domains in its tail region, although with unknown underlying molecular mechanisms. MyoX's first PH domain is split into halves by its second PH domain. We show here that the PH1(N)-PH2-PH1(C) tandem allows MyoX to bind to phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P(3)] with high specificity and cooperativity. We further show that PH2 is responsible for the specificity of the PI(3,4,5)P(3) interaction, whereas PH1 functions to enhance the lipid membrane-binding avidity of the tandem. The structure of the MyoX PH1(N)-PH2-PH1(C) tandem reveals that the split PH1, PH2, and the highly conserved interdomain linker sequences together form a rigid supramodule with two lipid-binding pockets positioned side by side for binding to phosphoinositide membrane bilayers with cooperativity. Finally, we demonstrate that disruption of PH2-mediated binding to PI(3,4,5)P(3) abolishes MyoX's function in inducing filopodial formation and elongation.

PubMed: 21965296
DOI: 10.1091/mbc.E11-04-0354

Experimental method

X-RAY DIFFRACTION (2.53 Å)