4LL6: Structure Of Myo4p Globular Tail Domain

Citation:
Proc. Natl. Acad. Sci. U. S. A. (2014) 111 p.E1082-E1090
Abstract
Myosin 4 protein (Myo4p), one of five distinct myosins of yeast, is dedicated to cytoplasmic transport of two types of cargos, zipcoded messenger ribonucleoprotein particles (mRNPs) and tubular endoplasmic reticulum (tER). Neither cargo binds directly to Myo4p. Instead, swi5p-dependent HO expression 3 protein (She3p) serves as an "adaptor" that contains three binding modules, one for Myo4p and one each for zipcoded mRNP and tER. The assembly of a transport-competent motor complex is poorly understood. Here, we report that Myo4p*She3p forms a stable 1:2 heterotrimer in solution. In the Myo4p*She3p crystal structure, Myo4p's C-terminal domain (CTD) assumes a lobster claw-shaped form, the minor prong of which adheres to a pseudocoiled-coil region of She3p. The extensive Myo4p*She3p interactome buries 3,812 A(2) surface area and is primarily hydrophobic. Because the Myo4p*She3p heterotrimer contains only one myosin molecule, it is not transport-competent. By stepwise reconstitution, we found a single molecule of synthetic oligonucleotide (representing the mRNA zipcode element) bound to a single tetramer of zipcode binding protein She2p to be sufficient for Myo4p*She3p dimerization. Therefore, cargo initiates cross-linking of two Myo4p*She3p heterotrimers to an ensemble that contains two myosin molecules obligatory for movement. An additional crystal structure comprising an overlapping upstream portion of She3p showed continuation of the pseudocoiled-coil structure and revealed another highly conserved surface region. We suggest this region as a candidate binding site for a yet unidentified tER ligand. We propose a model whereby zipcoded mRNP and/or tER ligands couple two Myo4p*She3p heterotrimers and thereby generate a transport-competent motor complex either for separate transport or cotransport of these two cargos.
PDB ID: 4LL6Download
MMDB ID: 117479
PDB Deposition Date: 2013/7/9
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 4LL6: monomeric; determined by author and by software (PISA)
Molecular Components in 4LL6
Label Count Molecule
Protein (1 molecule)
1
Myosin-4(Gene symbol: MYO4)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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