2P2T

Crystal structure of dynein light chain LC8 bound to residues 123-138 of intermediate chain IC74

Summary for 2P2T

• Entry DOI: 10.2210/pdb2p2t/pdb
• Related: 2P1K
• Descriptor: Dynein light chain 1, cytoplasmic, Dynein intermediate chain peptide, ACETATE ION, ... (5 entities in total)
• Functional Keywords: protein - peptide complex, transport protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Cellular location: Cytoplasm, cytoskeleton : Q24117; Cytoplasm, cytoskeleton . Isoform 2c: Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Isoform 2a: Nucleus membrane; Peripheral membrane protein; Cytoplasmic side. Isoform 2b: Nucleus membrane; Peripheral membrane protein; Cytoplasmic side: Q24246
• Total number of polymer chains: 2
• Total formula weight: 12258.84

Authors

Benison, G.,Karplus, P.A.,Barbar, E. (deposition date: 2007-03-07, release date: 2008-01-15, Last modification date: 2024-02-21)

Primary citation

Benison, G.,Karplus, P.A.,Barbar, E.
Structure and dynamics of LC8 complexes with KXTQT-motif peptides: swallow and dynein intermediate chain compete for a common site.
J.Mol.Biol., 371:457-468, 2007

PubMed Abstract: The dynein light chain LC8 is an integral subunit of the cytoplasmic dynein motor complex that binds directly to and promotes assembly of the dynein intermediate chain (IC). LC8 interacts also with a variety of putative dynein cargo molecules such as Bim, a proapoptotic Bcl2 family protein, which have the KXTQT recognition sequence and neuronal nitric oxide synthase (nNOS), which has the GIQVD fingerprint but shares the same binding grooves at the LC8 dimer interface. The work reported here investigates the interaction of LC8 with IC and a putative cargo, Swallow, which share the KXTQT recognition sequence, and addresses the apparent paradox of how LC8, as part of dynein, mediates binding to cargo. The structures of Drosophila LC8 bound to peptides from IC and Swallow solved by X-ray diffraction show that the IC and Swallow peptides bind in the same grooves at the dimer interface. Differences in flexibility between bound and free LC8 were evaluated from hydrogen isotope exchange experiments using heteronuclear NMR spectroscopy. Peptide binding causes an increase in protection from exchange primarily in residues that interact directly with the peptide, such as the beta-strand intertwined at the interface and the N-terminal end of helix alpha2. There is considerably more protection upon Swallow binding, consistent with tighter binding relative to IC. Comparison with the LC8/nNOS complex shows how both the GIQVD and KXTQT fingerprints are recognized in the same groove. The similar structures of LC8/IC and LC8/Swa and the tighter binding of Swallow call into question the role for LC8 as a cargo adaptor protein, and suggest that binding of LC8 to Swallow serves another function, possibly that of a dimerization engine, which is independent of its role in dynein.

PubMed: 17570393
DOI: 10.1016/j.jmb.2007.05.046

Experimental method

X-RAY DIFFRACTION (3 Å)