3AU4

Structure of the human myosin-X MyTH4-FERM cassette bound to its specific cargo, DCC

Summary for 3AU4

• Entry DOI: 10.2210/pdb3au4/pdb
• Related: 3AU5
• Descriptor: Myosin-X, Netrin receptor DCC (3 entities in total)
• Functional Keywords: protein-protein complex, motor protein cargo transportation, motor protein-apoptosis complex, motor protein/apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytosol: Q9HD67; Membrane; Single-pass type I membrane protein: P43146
• Total number of polymer chains: 2
• Total formula weight: 70148.81

Authors

Hirano, Y.,Hatano, T.,Hakoshima, T. (deposition date: 2011-01-28, release date: 2011-07-13, Last modification date: 2024-03-13)

Primary citation

Hirano, Y.,Hatano, T.,Takahashi, A.,Toriyama, M.,Inagaki, N.,Hakoshima, T.
Structural basis of cargo recognition by the myosin-X MyTH4-FERM domain
Embo J., 30:2734-2747, 2011

PubMed Abstract: Myosin-X is an important unconventional myosin that is critical for cargo transportation to filopodia tips and is also utilized in spindle assembly by interacting with microtubules. We present a series of structural and biochemical studies of the myosin-X tail domain cassette, consisting of myosin tail homology 4 (MyTH4) and FERM domains in complex with its specific cargo, a netrin receptor DCC (deleted in colorectal cancer). The MyTH4 domain is folded into a helical VHS-like structure and is associated with the FERM domain. We found an unexpected binding mode of the DCC peptide to the subdomain C groove of the FERM domain, which is distinct from previously reported β-β associations found in radixin-adhesion molecule complexes. We also revealed direct interactions between the MyTH4-FERM cassette and tubulin C-terminal acidic tails, and identified a positively charged patch of the MyTH4 domain, which is involved in tubulin binding. We demonstrated that both DCC and integrin bindings interfere with microtubule binding and that DCC binding interferes with integrin binding. Our results provide the molecular basis by which myosin-X facilitates alternative dual binding to cargos and microtubules.

PubMed: 21642953
DOI: 10.1038/emboj.2011.177

Experimental method

X-RAY DIFFRACTION (1.9 Å)