Model for the motor component of dynein heavy chain based on homology to the AAA family of oligomeric ATPases.
BACKGROUND
Recent iterative methods for sequence alignment have indicated that the 380 kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. These alignments indicate that the core of the 380 kDa motor unit contains a concatenated chain of six AAA modules, of which four correspond to the ATP binding sites with P-loop signatures described previously, and two are modules in which the P loop has been lost in evolution.


RESULTS
We report predicted structures for the six AAA modules in the beta heavy chain of axonemal dynein, based upon their homology to a template of structurally conserved regions derived from three AAA proteins with experimentally determined structures (pdb:1A5T, pdb:1DOO, and pdb:1NSF). The secondary structural elements of the AAA modules in dynein correspond to regions of sequence that are relatively well conserved in different dynein isoforms. The tertiary structure of each AAA module comprises a major alpha/beta N domain from which a smaller all-alpha C domain protrudes at an angle, as part of the putative nucleotide binding cavity. The structures of the six modules are assembled into a ring, approximately 125 A in diameter, that resembles the structure of the dynein motor unit observed by electron microscopy.


CONCLUSIONS
The predicted structures are supported by procedures that assess global, regional, and local quality, with the module containing the hydrolytic ATP binding site being supported the most strongly. The structural resemblance of the dynein motor to the hexameric assembly of AAA modules in the hsp100 family of chaperones suggests that the basic mechanism underlying the ATP-dependent translocation of dynein along a microtubule may have aspects in common with the ATP-dependent translocation of polypeptides into the interior compartment of chaperones.
Biotechnology/Molecular Biology Instrumentation, Training Facility, Pacific Biomedical Research Center, University of Hawaii, Honolulu, 96822, Honolulu, HI, USA.
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Gibbons
D049069:ATP-Dependent Proteases; D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D004258:DNA Polymerase III / Q000737:chemistry; D004398:Dyneins / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins; D017433:Protein Structure, Secondary; D012617:Sea Urchins / Q000737:chemistry; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D033921:Vesicular Transport Proteins; D000255:Adenosine Triphosphate; D004258:DNA Polymerase III; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; D004398:Dyneins; D052066:N-Ethylmaleimide-Sensitive Proteins