PDBsum entry 4ck5

Motor protein

PDB id: 4ck5

Contents

Protein chains

412 a.a.*

426 a.a.*

350 a.a.*

Ligands

GTP

GDP

TA1

ADP

Metals

_MG

* C-alpha coords only

PDB id:

4ck5

Name:

Motor protein

Title:

Pseudo-atomic model of microtubule-bound human kinesin-5 motor domain in the adp state, based on cryo-electron microscopy experiment.

Structure:

Tubulin alpha-1d chain. Chain: a. Synonym: alpha tubulin. Tubulin beta-2b chain. Chain: b. Synonym: beta tubulin. Kinesin-like protein kif11. Chain: c. Fragment: motor domain, residues 1-367.

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: brain. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Authors:

A.Goulet,J.Major,Y.Jun,S.Gross,S.Rosenfeld,C.Moores

Key ref:

A.Goulet et al. (2014). Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family. Proc Natl Acad Sci U S A, 111, 1837-1842. PubMed id: 24449904 DOI: 10.1073/pnas.1319848111

Date:

30-Dec-13 Release date: 05-Feb-14

Protein chain

Q2HJ86  (TBA1D_BOVIN) -  Tubulin alpha-1D chain from Bos taurus

Seq: 452 a.a.

Struc: 412 a.a.*

Protein chain

Q6B856  (TBB2B_BOVIN) -  Tubulin beta-2B chain from Bos taurus

Seq: 445 a.a.

Struc: 426 a.a.*

Protein chain

P52732  (KIF11_HUMAN) -  Kinesin-like protein KIF11 from Homo sapiens

Seq: 1056 a.a.

Struc: 350 a.a.*

* PDB and UniProt seqs differ at 16 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.6.5.- - ?????
• Enzyme class 3: Chains B, C: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1073/pnas.1319848111

Proc Natl Acad Sci U S A 111:1837-1842 (2014)

PubMed id: 24449904

Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family.

A.Goulet, J.Major, Y.Jun, S.P.Gross, S.S.Rosenfeld, C.A.Moores.

ABSTRACT

Kinesins are responsible for a wide variety of microtubule-based, ATP-dependent functions. Their motor domain drives these activities, but the molecular adaptations that specify these diverse and essential cellular activities are poorly understood. It has been assumed that the first identified kinesin-the transport motor kinesin-1-is the mechanistic paradigm for the entire superfamily, but accumulating evidence suggests otherwise. To address the deficits in our understanding of the molecular basis of functional divergence within the kinesin superfamily, we studied kinesin-5s, which are essential mitotic motors whose inhibition blocks cell division. Using cryo-electron microscopy and determination of structure at subnanometer resolution, we have visualized conformations of microtubule-bound human kinesin-5 motor domain at successive steps in its ATPase cycle. After ATP hydrolysis, nucleotide-dependent conformational changes in the active site are allosterically propagated into rotations of the motor domain and uncurling of the drug-binding loop L5. In addition, the mechanical neck-linker element that is crucial for motor stepping undergoes discrete, ordered displacements. We also observed large reorientations of the motor N terminus that indicate its importance for kinesin-5 function through control of neck-linker conformation. A kinesin-5 mutant lacking this N terminus is enzymatically active, and ATP-dependent neck-linker movement and motility are defective, although not ablated. All these aspects of kinesin-5 mechanochemistry are distinct from kinesin-1. Our findings directly demonstrate the regulatory role of the kinesin-5 N terminus in collaboration with the motor's structured neck-linker and highlight the multiple adaptations within kinesin motor domains that tune their mechanochemistries according to distinct functional requirements.