PDBsum entry: 2hxh

Transport protein

PDB id: 2hxh

Contents

Protein chains

412 a.a. *

426 a.a. *

330 a.a. *

Ligands

GTP

GDP

TA1

ADP

Metals

_MG ×2

* Residue conservation analysis

PDB id:

2hxh

Name:

Transport protein

Title:

Kif1a head-microtubule complex structure in adp-form

Structure:

Tubulin alpha chain. Chain: a. Tubulin beta chain. Chain: b. Kinesin-like protein kif1a. Chain: c. Fragment: kif1a head domain. Synonym: axonal transporter of synaptic vesicles. Engineered: yes.

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Mus musculus. House mouse. Organism_taxid: 10090. Gene: kif1a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Trimer (from PQS)

Authors:

M.Kikkawa,N.Hirokawa

Key ref:

M.Kikkawa and N.Hirokawa (2006). High-resolution cryo-EM maps show the nucleotide binding pocket of KIF1A in open and closed conformations. EMBO J, 25, 4187-4194. PubMed id: 16946706 DOI: 10.1038/sj.emboj.7601299

Date:

03-Aug-06 Release date: 10-Oct-06

Protein chain

P02550  (TBA1A_PIG) -  Tubulin alpha-1A chain

Seq: 451 a.a.

Struc: 412 a.a.

Protein chain

P02554  (TBB_PIG) -  Tubulin beta chain

Seq: 445 a.a.

Struc: 426 a.a.

Protein chain

P33173  (KIF1A_MOUSE) -  Kinesin-like protein KIF1A

Seq: 1695 a.a.

Struc: 330 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: protein complex (2 terms)
• Biological process: microtubule-based process (4 terms)
• Biochemical function: structural molecule activity (6 terms)

DOI no: 10.1038/sj.emboj.7601299

EMBO J 25:4187-4194 (2006)

PubMed id: 16946706

High-resolution cryo-EM maps show the nucleotide binding pocket of KIF1A in open and closed conformations.

M.Kikkawa, N.Hirokawa.

ABSTRACT

Kinesin is an ATP-driven microtubule (MT)-based motor fundamental to organelle transport. Although a number of kinesin crystal structures have been solved, the structural evidence for coupling between the bound nucleotide and the conformation of kinesin is elusive. In addition, the structural basis of the MT-induced ATPase activity of kinesin is not clear because of the absence of the MT in the structure. Here, we report cryo-electron microscopy structures of the monomeric kinesin KIF1A-MT complex in two nucleotide states at about 10 A resolution, sufficient to reveal the secondary structure. These high-resolution maps visualized clear structural changes that suggest a mechanical pathway from the nucleotide to the neck linker via the motor core rotation. In addition, new nucleotide binding pocket conformations are observed that are different from X-ray crystallographic structures; it is closed in the 5'-adenylyl-imidodiphosphate state, but open in the ADP state. These results suggest a structural model of biased diffusion movement of monomeric kinesin motor.

Selected figure(s)

Figure 2.
Figure 2 Cryo-EM maps of KIF1A–MT complexes in the ADP (A, C, E) and AMPPNP states (B, D, F). (A, B) Isosurface representation of KIF1A–MT complexes. (C–F) Fitting of the X-ray crystal structures into cryo-EM maps. MTs are shown with their plus-end up and assignment of - and -tubulin is based on that of Krebs et al (2004). The blue chickenwires are contoured at 0.7 of the density map, with a mesh size of 1 Å. A 20.6° rotation around the axis shown in (D) and (F) explains conformational changes of the kinesin core from the ADP state to the AMPPNP state.

Figure 5.
Figure 5 MT-centric superposition of the ADP and AMPPNP KIF1A crystal structures from KIF1A–MT complexes, presenting interactions between KIF1A residues and tubulin. Interacting residues observed in ADP (orange), AMPPNP (red) or both complexes (black) are depicted with lines connecting to the corresponding tubulin-binding site.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 4187-4194) copyright 2006.

Figures were selected by the author.