5jpw
From Proteopedia
Molecular basis for protein recognition specificity of the DYNLT1/Tctex1 canonical binding groove. Characterization of the interaction with activin receptor IIB
Structural highlights
Function[DYLT1_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia. Is involved in intracellular targeting of D-type retrovirus gag polyproteins to the cytoplasmic assembly site. May also be a accessory component of axonemal dynein.[1] Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Involved in the regulation of mitotic spindle orientation (By similarity). Publication Abstract from PubMedIt has been suggested that DYNLT1, a dynein light chain known to bind to various cellular and viral proteins, can function both as a molecular clamp and as a microtubule-cargo adapter. Recent data have shown that the DYNLT1 homodimer binds to two dynein intermediate chains to subsequently link cargo proteins, such as the guanine nucleotide exchange factor Lfc or the small GTPases RagA and Rab3D. Although over twenty DYNLT1-interacting proteins have been reported, the exact sequence requirements that enable their association to the canonical binding groove or to the secondary site within the DYNLT1 surface are unknown. We describe herein the sequence recognition properties of the hydrophobic groove of DYNLT1 known to accommodate dynein intermediate chain. Using a pepscan approach we have substituted each amino acid within the interacting peptide for all 20 natural amino acids and we have identified novel binding sequences. Our data led us to propose Activin Receptor IIB as a novel DYNLT1 ligand and suggest that DYNLT1 functions as a molecular dimerization engine bringing together two receptor monomers in the cytoplasmic side of the membrane. In addition, we provide evidence regarding a dual binding mode adopted by certain interacting partners such as Lfc or the Parathyroid Hormone Receptor. Finally, we have used NMR spectroscopy to obtain the solution structure of human DYNLT1 forming a complex with DIC, being the first mammalian structure available. Molecular Basis for the Protein Recognition Specificity of the dynein light chain DYNLT1/Tctex1. Characterization of the Interaction with Activin Receptor IIB.,Merino-Gracia J, Zamora-Carreras H, Bruix M, Rodriguez-Crespo I J Biol Chem. 2016 Aug 8. pii: jbc.M116.736884. PMID:27502274[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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