5JPW

Molecular basis for protein recognition specificity of the DYNLT1/Tctex1 canonical binding groove. Characterization of the interaction with activin receptor IIB

Summary for 5JPW

• Entry DOI: 10.2210/pdb5jpw/pdb
• NMR Information: BMRB: 30074
• Descriptor: Dynein light chain Tctex-type 1,Cytoplasmic dynein 1 intermediate chain 2 (1 entity in total)
• Functional Keywords: dnylt1/tctex-1; dynein intermediate chain; dynein motor; dynein-mediated transport, motor protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30862.80

Authors

Rodriguez-Crespo, I.,Merino-Gracia, J.,Bruix, M.,Zamora-Carreras, H. (deposition date: 2016-05-04, release date: 2016-08-17, Last modification date: 2024-07-03)

Primary citation

Merino-Gracia, J.,Zamora-Carreras, H.,Bruix, M.,Rodriguez-Crespo, I.
Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain DYNLT1/Tctex1: CHARACTERIZATION OF THE INTERACTION WITH ACTIVIN RECEPTOR IIB.
J.Biol.Chem., 291:20962-20975, 2016

PubMed Abstract: It 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 20 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 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 dynein intermediate chain of ∼74 kDa; it is the first mammalian structure available.

PubMed: 27502274
DOI: 10.1074/jbc.M116.736884

Experimental method

SOLUTION NMR