PDBsum entry 2ncd

Contractile protein

PDB id: 2ncd

Contents

Protein chain

358 a.a. *

Ligands

SO4 ×4

ADP

Waters ×54

* Residue conservation analysis

PDB id:

2ncd

Name:

Contractile protein

Title:

Ncd (non-claret disjunctional) dimer from d. Melanogaster

Structure:

Protein (kinesin motor ncd). Chain: a. Fragment: residues 281-700. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: ncd. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: bacterial expression

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.226 R-free: 0.270

Authors:

E.P.Sablin,R.B.Case,S.C.Dai,C.L.Hart,A.Ruby,R.D.Vale,R.J.Fletterick

Key ref:

E.P.Sablin et al. (1998). Direction determination in the minus-end-directed kinesin motor ncd. Nature, 395, 813-816. PubMed id: 9796817 DOI: 10.1038/27463

Date:

04-Jun-99 Release date: 09-Jun-99

Protein chain

P20480  (NCD_DROME) -  Protein claret segregational from Drosophila melanogaster

Seq: 700 a.a.

Struc: 358 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.4.- - ?????

DOI no: 10.1038/27463

Nature 395:813-816 (1998)

PubMed id: 9796817

Direction determination in the minus-end-directed kinesin motor ncd.

E.P.Sablin, R.B.Case, S.C.Dai, C.L.Hart, A.Ruby, R.D.Vale, R.J.Fletterick.

ABSTRACT

Motor proteins of the kinesin superfamily transport intracellular cargo along microtubules. Although different kinesin proteins share 30-50% amino-acid identity in their motor catalytic cores, some move to the plus end of microtubules whereas others travel in the opposite direction. Crystal structures of the catalytic cores of conventional kinesin (a plus-end-directed motor involved in organelle transport) and ncd (a minus-end-directed motor involved in chromosome segregation) are nearly identical; therefore, the structural basis for their opposite directions of movement is unknown. Here we show that the ncd 'neck' made up of 13 class-specific residues next to the superfamily-conserved catalytic core, is essential for minus-end-directed motility, as mutagenesis of these neck residues reverses the direction of ncd motion. By solving the 2.5 A structure of a functional ncd dimer, we show that the ncd neck (a coiled-coil) differs from the corresponding region in the kinesin neck (an interrupted beta-strand), although both necks interact with similar elements in the catalytic cores. The distinct neck architectures also confer different symmetries to the ncd and kinesin dimers and position these motors with appropriate directional bias on the microtubule.

Selected figure(s)

Figure 2.
Figure 2 Architecture of the ncd neck-core interface. a, Interactions of the neck with the motor heads: the neck is shown in purple; regions of the core that contact the neck are shown in blue ( 1), magenta (L6), green (L10) and yellow (L13); and the stalk domain is golden. Loop L13 is next to the predicted microtubule (MT)-binding site of ncd (loop L12 and helix 5). Bound ADP is shown as green spheres. b, The interdomain contacts; the colouring scheme for the interacting residues in the core is consistent with a.

Figure 3.
Figure 3 Model showing the ncd and kinesin dimer structures docked onto a tubulin protofilament. The colouring scheme for the parts of the kinesin and ncd dimers is consistent with Fig. 1. The bound ncd and kinesin heads are positioned similarly, with loop L12 (red) docked onto the tubulin (background). Because of the distinct architectures of the kinesin and ncd necks, the unbound kinesin head points towards the plus end, whereas the unbound ncd head is tilted towards the minus end of the protofilament.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 395, 813-816) copyright 1998.

Figures were selected by the author.