Kinesin: switch I & II and the motor mechanism.
New crystal structures of the kinesin motors differ from previously described motor-ADP atomic models, showing striking changes both in the switch I region near the nucleotide-binding cleft and in the switch II or 'relay' helix at the filament-binding face of the motor. The switch I region, present as a short helix flanked by two loops in previous motor-ADP structures, rearranges into a pseudo-beta-hairpin or is completely disordered with melted helices to either side of the disordered switch I loop. The relay helix undergoes a rotational movement coupled to a translation that differs from the piston-like movement of the relay helix observed in myosin. The changes observed in the crystal structures are interpreted to represent structural transitions that occur in the kinesin motors during the ATP hydrolysis cycle. The movements of switch I residues disrupt the water-mediated coordination of the bound Mg2+, which could result in loss of Mg2+ and ADP, raising the intriguing possibility that disruption of the switch I region leads to release of nucleotide by the kinesins. None of the new structures is a true motor-ATP state, however, probably because conformational changes at the active site of the kinesins require interactions with microtubules to stabilize the movements.
Kull
F Jon
FJ
Department of Biophysics, Max-Planck Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany.
Endow
Sharyn A
SA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D020409:Molecular Motor Proteins; D009711:Nucleotides; D000255:Adenosine Triphosphate; D009218:Myosins; D016547:Kinesins; D008274:Magnesium