Taxonomic distribution of proteins containing KISc domains

The KISc domain within your query sequence starts at position and ends at position , and its E-value is < 1e-12.

Nucleotide-dependent conformations of the kinesin dimer interacting with microtubules.

Arnal I, Wade RH
Structure. 1998; 6: 33-8

BACKGROUND: Kinesins are crucial to eukaryotic cells. They are a superfamily of motor proteins that use ATP hydrolysis to move along microtubules. Many of these motors are heterotetramers with two heavy and two light chains. The heavy chain has a globular motor domain that interacts with microtubules and shows a similar sequence throughout the family. Compared with myosin and dynein, kinesin provides a 'simple' model for understanding molecular motors. RESULTS: Electron cryomicroscopy and three-dimensional reconstruction methods have been used to investigate microtubule-kinesin dimer complexes in different nucleotide states. Three-dimensional maps were obtained in the presence of 5'-adenylylimidodiphosphate (AMP-PNP), ADP-AIF4, ADP and apyrase. In all cases, kinesin has one attached and one free head per tubulin heterodimer. The attached heads appear very similar whereas the free heads show distinct conformations and orientations depending on their nucleotide states. CONCLUSIONS: The kinesin dimer is likely to undergo considerable conformational changes during its ATP hydrolysis cycle. In all nucleotide states, the kinesin dimer attaches to a microtubule using one motor domain with the other motor domain hanging free. Only the free domain changes conformation in the presence of different nucleotides, suggesting that it, or the region linking both motor domains to the coiled coil, is the determinant of directionality. These results give some structural clues as to how kinesin moves along microtubules and we describe possible models of kinesin movement based on currently available data.

Kinesin: what gives?

Block SM
Cell. 1998; 93: 5-8

Leading the procession: new insights into kinesin motors.

Block SM
J Cell Biol. 1998; 140: 1281-4

Kinesin and dynein superfamily proteins and the mechanism of organelle transport.

Hirokawa N
Science. 1998; 279: 519-26

Cells transport and sort proteins and lipids, after their synthesis, to various destinations at appropriate velocities in membranous organelles and protein complexes. Intracellular transport is thus fundamental to cellular morphogenesis and functioning. Microtubules serve as a rail on which motor proteins, such as kinesin and dynein superfamily proteins, convey their cargoes. This review focuses on the molecular mechanism of organelle transport in cells and describes kinesin and dynein superfamily proteins.

Molecular motors: the natural economy of kinesin.

Cross RA
Curr Biol. 1997; 7: 6313-6313

Kinesin is a molecular-scale walking machine. New analyses of its mechanism indicate that each step along a microtubule consumes one ATP molecule, and that the binding and cleavage of ATP precede detachment of the molecule's 'feet'. Directional walking ensues if ATP processing occurs preferentially on one foot.

The mechanisms of fast and slow transport in neurons: identification and characterization of the new kinesin superfamily motors.

Hirokawa N
Curr Opin Neurobiol. 1997; 7: 605-14

Progress in the identification and characterization of new carboxy-terminal motor domain type kinesin superfamily proteins (KIFs)-KIFC2, 16 new KIFs and KIF-associated protein 3 (KAP3)-has provided further insight into the molecular mechanisms of organelle transport in neurons. Developments in molecular and cellular biophysics and recombinant adenovirus infection techniques combined with transgenic mice technology have enhanced the visualization of moving forms of cytoskeletal proteins during slow transport. The results of these studies strongly support the subunit transport theory.

The crystal structure of dimeric kinesin and implications for microtubule-dependent motility.

Kozielski F, Sack S, Marx A, Thormahlen M, Schonbrunn E, Biou V, Thompson A, Mandelkow EM, Mandelkow E
Cell. 1997; 91: 985-94

The dimeric form of the kinesin motor and neck domain from rat brain with bound ADP has been solved by X-ray crystallography. The two heads of the dimer are connected via a coiled-coil alpha-helical interaction of their necks. They are broadly similar to one another; differences are most apparent in the head-neck junction and in a moderate reorientation of the neck helices in order to adopt to the coiled-coil conformation. The heads show a rotational symmetry (approximately 120 degrees) about an axis close to that of the coiled-coil. This arrangement is unexpected since it is not compatible with the microtubule lattice. In this arrangement, the two heads of a kinesin dimer could not have equivalent interactions with microtubules.

X-ray structure of motor and neck domains from rat brain kinesin.

Sack S, Muller J, Marx A, Thormahlen M, Mandelkow EM, Brady ST, Mandelkow E
Biochemistry. 1997; 36: 16155-65

We have determined the X-ray structure of rat kinesin head and neck domains. The folding of the core motor domain resembles that of human kinesin reported recently [Kull, F. J., et al. (1996) Nature 380, 550-554]. Novel features of the structure include the N-terminal region, folded as a beta-strand, and the C-terminal transition from the motor to the rod domain, folded as two beta-strands plus an alpha-helix. This helix is the beginning of kinesin's neck responsible for dimerization of the motor complex and for force transduction. Although the folding of the motor domain core is similar to that of a domain of myosin (an actin-dependent motor), the position and angle of kinesin's neck are very different from those of myosin's stalk, suggesting that the two motors have different mechanisms of force transduction. The N- and C-terminal ends of the core motor, thought to be responsible for the directionality of the motors [Case, R. B., et al. (1997) Cell 90, 959-966], take the form of beta-strands attached to the central beta-sheet of the structure.

The design plan of kinesin motors.

Vale RD, Fletterick RJ
Annu Rev Cell Dev Biol. 1997; 13: 745-77

The kinesin superfamily comprises a large and structurally diverse group of microtubule-based motor proteins that produce a variety of force-generating activities within cells. This review addresses how the structures of kinesin proteins provide clues as to their biological functions and motile properties. We discuss structural features common to all kinesin motors, as well as specialized features that enable subfamilies of related motors to carry out specialized activities. We also discuss how the kinesin motor domain uses chemical energy from ATP hydrolysis to move along microtubules.

Crystal structure of the kinesin motor domain reveals a structural similarity to myosin.

Kull FJ, Sablin EP, Lau R, Fletterick RJ, Vale RD
Nature. 1996; 380: 550-5

Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation. It has two identical approximately 960-amino-acid chains containing an amino-terminal globular motor domain, a central alpha-helical region that enables dimer formation through a coiled-coil, and a carboxy-terminal tail domain that binds light chains and possibly an organelle receptor. The kinesin motor domain of approximately 340 amino acids, which can produce movement in vitro, is much smaller than that of myosin (approximately 850 amino acids) and dynein (1,000 amino acids), and is the smallest known molecular motor. Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography. The motor consists primarily of a single alpha/beta arrowhead-shaped domain with dimensions of 70 x 45 x 45 A. Unexpectedly, it has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence++ identity, and exhibit distinct enzymatic and motile properties, our results suggest that these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.

Kinesin proteins: a phylum of motors for microtubule-based motility.

Moore JD, Endow SA
Bioessays. 1996; 18: 207-19

The cellular processes of transport, division and, possibly, early development all involve microtubule-based motors. Recent work shows that, unexpectedly, many of these cellular functions are carried out by different types of kinesin and kinesin-related motor proteins. The kinesin proteins are a large and rapidly growing family of microtubule-motor proteins that share a 340-amino-acid motor domain. Phylogenetic analysis of the conserved motor domains groups the kinesin proteins into a number of subfamilies, the members of which exhibit a common molecular organization and related functions. The kinesin proteins that belong to different subfamilies differ in their rates and polarity of movement along microtubules, and probably in the particles/organelles that they transport. The kinesins arose early in eukaryotic evolution and gene duplication has allowed functional specialization to occur, resulting in a surprisingly large number of different classes of these proteins adapted for intracellular transport of vesicles and organelles, and for assembly and force generation in the meiotic and mitotic spindles.

Kinesin and myosin: molecular motors with similar engines.

Rayment I
Structure. 1996; 4: 501-4

Structure determination of the catalytic domains of two members of the kinesin superfamily reveals that this class of molecular motor exhibits the same architecture as myosin and suggests that these microtubule- and actin-based motors arose from a common ancestor.

X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution.

Smith CA, Rayment I
Biochemistry. 1996; 35: 5404-17

The structure of the vanadate-trapped ADP complex of a truncated head of Dictyostelium myosin II consisting of residues Asp 2-Asn 762 has been determined by molecular replacement at 1.9 A resolution and refined to a crystallographic R-factor of 19.4%. The crystals belong to the orthorhombic space group C2221 where a = 84.50 A, b = 145.4 A, and c = 152.8 A. The conformation of the protein is similar to that of MgADP.AlF4.SlDc [Fisher, A.J., et al. (1995) Biochemistry 34, 8960-8972]. The nucleotide binding site contains a complex between MgADP and vanadate where MgADP exhibits a very similar conformation to that seen in previous complexes. The vanadate ion adopts a trigonal bipyramidal coordination. The three equatorial oxygen ligands are fairly short, average 1.7 A, relative to a single bond distance of approximately 1.8 A and are coordinated to the magnesium ion, N zeta of Lys 185, and five other protein ligands. The apical coordination to the vanadate ion is filled by a terminal oxygen on the beta-phosphate of ADP and a water molecule at bond distances of 2.1 and 2.3 A, respectively. The long length of the apical bonds suggests that the bond order is considerably less than unity. This structure confirms the earlier suggestion that vanadate is a model for the transition state of ATP hydrolysis and thus provides insight into those factors that are responsible for catalysis. In particular, it shows that the protein ligands and water structure surrounding the gamma-phosphate pocket are oriented to stabilize a water molecule in an appropriate position for in-line nucleophilic attack on the gamma-phosphorus of ATP. This structure reveals also an orientation of the COOH-terminal region beyond Thr 688 which is very different from that observed in either MgADP.BeFx.SlDc or chicken skeletal myosin subfragment 1. This is consistent with the COOH-terminal region of the molecule playing an important role in the transduction of chemical energy of hydrolysis of ATP into mechanical movement.

Motor proteins 1: kinesins.

Bloom GS, Endow SA
Protein Profile. 1995; 2: 1105-71

Progress regarding the kinesins is now being made at a rapid and accelerating rate. The in vivo-functions, and biophysical and enzymatic properties of kinesin itself are being explored at ever increasing levels of detail. The kinesin-related proteins now number several dozen, and although more is known about primary structure than function for most of the proteins, this trend is already reversing. For example, knowledge about the kinesin-related protein, ncd, is expanding rapidly, and more is already known about its three-dimensional structure than is known for kinesin heavy chain. This volume presents a comprehensive review of the major published works on kinesin and kinesin-related proteins. Hopefully, this manuscript will complement other recent review articles [17, 20, 25, 37, 60-62, 67, 69, 75, 85-88, 231, 233, 238, 244, 269-271, 281, 282, 292] or books [49, 227, 293] that have focused on more selective aspects of the kinesin family, or have been aimed more generally at MT motor proteins. In line with the stated purpose of the Protein Profile series, annual updates of the review on the kinesins are planned for at least the next few years.

X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-.

Fisher AJ, Smith CA, Thoden JB, Smith R, Sutoh K, Holden HM, Rayment I
Biochemistry. 1995; 34: 8960-72

The three-dimensional structures of the truncated myosin head from Dictyostelium discoideum myosin II complexed with beryllium and aluminum fluoride and magnesium ADP are reported at 2.0 and 2.6 A resolution, respectively. Crystals of the beryllium fluoride-MgADP complex belong to space group P2(1)2(1)2 with unit cell parameters of a = 105.3 A, b = 182.6 A, and c = 54.7 A, whereas the crystals of the aluminum fluoride complex belong to the orthorhombic space group C222(1) with unit cell dimensions of a = 87.9 A, b = 149.0 A, and c = 153.8 A. Chemical modification was not necessary to obtain these crystals. These structures reveal the location of the nucleotide complexes and define the amino acid residues that form the active site. The tertiary structure of the protein complexed with MgADP.BeFx is essentially identical to that observed previously in the three-dimensional model of chicken skeletal muscle myosin subfragment-1 in which no nucleotide was present. By contrast, the complex with MgADP.AlF4- exhibits significant domain movements. The structures suggest that the MgADP.BeFx complex mimics the ATP bound state and the MgADP.AlF4- complex is an analog of the transition state for hydrolysis. The domain movements observed in the MgADP.AlF4- complex indicate that myosin undergoes a conformational change during hydrolysis that is not associated with the nucleotide binding pocket but rather occurs in the COOH-terminal segment of the myosin motor domain.

X-ray structure of the magnesium(II)-pyrophosphate complex of the truncated head of Dictyostelium discoideum myosin to 2.7 A resolution.

Smith CA, Rayment I
Biochemistry. 1995; 34: 8973-81

The structure of the magnesium pyrophosphate complex of the truncated head of Dictyostelium myosin has been determined by molecular replacement at 2.7 A resolution and refined to a crystallographic R-factor of 16.0%. The crystals belong to the orthorhombic space group P2(1)2(1)2, where a = 105.2 A, b = 182.1 A, and c = 54.5 A. The conformation of the protein around the magnesium pyrophosphate is very similar to that seen when magnesium ADP-beryllium fluoride binds in the active site. The latter complex mimics the binding of ATP prior to hydrolysis. The pyrophosphate molecule occupies the beta- and gamma-phosphate sites, where the two phosphorus atoms are in the same positions as the beta-phosphate and the BeFx moiety of the beryllium fluoride-trapped ADP. The surrounding active site residues are almost perfectly superimposable in the two structures and the hydrogen-bonding interactions that the PPi makes with the protein are essentially identical. The similarity between the MgPPi and MgADP.BeFx complex with S1Dc suggests that the conformational change, which occurs when ATP binds to actomyosin and which reduces the affinity of myosin for actin, is caused by the binding of the gamma- and beta-phosphate groups of the nucleotide. This then implies that the role of the remainder of the substrate is to increase the binding affinity for myosin and thus to drive the equilibrium toward dissociation of myosin from actin.

The three-dimensional structure of a molecular motor.

Rayment I, Holden HM
Trends Biochem Sci. 1994; 19: 129-34

Myosin is one of only three proteins known to convert chemical energy into mechanical work. Although the chemical, kinetic and physiological characteristics of this protein have been studied extensively, it has been difficult to define its molecular basis of movement. With the recent X-ray structural determination of the myosin head, however, it is now possible to put forward a hypothesis on how myosin might function as a molecular motor.