6b9h

From Proteopedia

Complex of Hook Domain with a Dynein Light Intermediate Chain Peptide

PDB ID 6b9h

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Structural highlights

6b9h is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HOOK3_HUMAN Probably serves as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in cells. Dynein processivity and cargo selectivity depend on cargo-specific effectors that, while generally unrelated, share the ability to interact with dynein and dynactin to form processive dynein-dynactin-effector complexes. How this is achieved is poorly understood. Here, we identify a conserved region of the dynein Light Intermediate Chain 1 (LIC1) that mediates interactions with unrelated dynein-dynactin effectors. Quantitative binding studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly. A structure of the LIC1 helix bound to the N-terminal Hook domain reveals a conformational change that creates a hydrophobic cleft for binding of the LIC1 helix. The LIC1 helix competitively inhibits processive dynein-dynactin-effector motility in vitro, whereas structure-inspired mutations in this helix impair lysosomal positioning in cells. The results reveal a conserved mechanism of effector interaction with dynein-dynactin necessary for processive motility.

A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity.,Lee IG, Olenick MA, Boczkowska M, Franzini-Armstrong C, Holzbaur ELF, Dominguez R Nat Commun. 2018 Mar 7;9(1):986. doi: 10.1038/s41467-018-03412-8. PMID:29515126^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Walenta JH, Didier AJ, Liu X, Kramer H. The Golgi-associated hook3 protein is a member of a novel family of microtubule-binding proteins. J Cell Biol. 2001 Mar 5;152(5):923-34. PMID:11238449
↑ Sano H, Ishino M, Kramer H, Shimizu T, Mitsuzawa H, Nishitani C, Kuroki Y. The microtubule-binding protein Hook3 interacts with a cytoplasmic domain of scavenger receptor A. J Biol Chem. 2007 Mar 16;282(11):7973-81. Epub 2007 Jan 19. PMID:17237231 doi:http://dx.doi.org/10.1074/jbc.M611537200
↑ Xu L, Sowa ME, Chen J, Li X, Gygi SP, Harper JW. An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Mol Biol Cell. 2008 Dec;19(12):5059-71. Epub 2008 Sep 17. PMID:18799622 doi:http://dx.doi.org/E08-05-0473
↑ Lee IG, Olenick MA, Boczkowska M, Franzini-Armstrong C, Holzbaur ELF, Dominguez R. A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Nat Commun. 2018 Mar 7;9(1):986. doi: 10.1038/s41467-018-03412-8. PMID:29515126 doi:http://dx.doi.org/10.1038/s41467-018-03412-8