PDBsum entry 6b9h

Protein transport/motor protein

PDB id: 6b9h

Contents

Protein chains

151 a.a.

14 a.a.

Waters ×121

PDB id:

6b9h

Name:

Protein transport/motor protein

Title:

Complex of hook domain with a dynein light intermediate chain peptide

Structure:

Protein hook homolog 3. Chain: a. Synonym: hhk3. Engineered: yes. Cytoplasmic dynein 1 light intermediate chain 1. Chain: b. Synonym: lic1,dynein light chain a,dlc-a,dynein light intermediate chain 1,cytosolic. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hook3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.50Å R-factor: 0.156 R-free: 0.179

Authors:

I.G.Lee,R.Dominguez

Key ref:

I.G.Lee et al. (2018). A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Nat Commun, 9, 986. PubMed id: 29515126

Date:

10-Oct-17 Release date: 21-Mar-18

Protein chain

Q86VS8  (HOOK3_HUMAN) -  Protein Hook homolog 3 from Homo sapiens

Seq: 718 a.a.

Struc: 151 a.a.

Protein chain

Q9Y6G9  (DC1L1_HUMAN) -  Cytoplasmic dynein 1 light intermediate chain 1 from Homo sapiens

Seq: 523 a.a.

Struc: 14 a.a.

Nat Commun 9:986 (2018)

PubMed id: 29515126

A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity.

I.G.Lee, M.A.Olenick, M.Boczkowska, C.Franzini-Armstrong, E.L.F.Holzbaur, R.Dominguez.

ABSTRACT

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.