Kinesins comparing structures

Microtubules are the intracellular tracks for two classes of motor proteins kinesins and dyneins. During the past few years, the motor domain structures of several kinesins from different organisms have been determined by X-ray crystallography. Compared with kinesins, dyneins are much larger proteins and attempts to crystallize them have failed so far. Structural information about these proteins comes mosdy from electron microscopy. In this chapter, we mainly focus on the crystal structures of kinesin motor domains. 

In spite of the gross conformational differences between the Ned dimers, there are only minor differences between the individual motor domains. The overall fold of the motor domain is very similar to that of kinesin-1 and other N-type motors. Major differences are (1) The N-terminal lobe of Ned is enlarged (+9 amino acids) compared with rat kinesin-1. The additional residues are located between /11b and /11c (the L2 finger ). This, however, does not result in a simple elongation of the /1-hairpin as in HsKSP and in M-type motors (see below). In fact, the tip of the L2 finger is rather broadened and forms a short a-helix. (2) Loop L5, the insert in the P-loop helix z 2. is quite short (approximately eight residues compared with 12 in rat kinesin-1), due to three residues that are missing in the primary structure of DmNcd. (3) Switch-1 helix z.3 is short and loop L9, the linker between z.3 and / 6 that includes the switch-1... 

Explain how small structural differences can cause ncd protein to have reversed polarity compared "with normal kinesins. 

Unlike macroscopic machines, biomolecules constantly experience substantial fluctuations in their structures. Compared to the thermal energy, an individual nonco-valent bond is only marginally stable. Thus, biomolecules can partially unfold and refold if this dynamics is more effectively exploited to achieve their functional goal. Kinesins also adopt this strategy to effectively march along the MT. 

In addition to myosin, it is of interest to use the similar techniques to analyze other molecular motors in a comparative fashion. Of particular interest are kinesin and helicases, in which the chanical step occurs when the motor is bound on its tracks therefore, it is possible that somewhat different sets of constraints and structural features can be found in these motors compared to myosin. Once mechanochemical coupling is weU understood in several representative systems, it might be possible to design computational protocols that allow one to predict conformational transitions coupled to ATP binding and/or hydrolysis based on, for example, combination of experimental data at different resolutions (e.g., x-ray and electron microscopy [EM], fluorescence resonance energy transfer [FRET]) meeting this challenge can have a... 

Other than the above structural features there are two important and exclusive properties that make DNA suitable for molecular level constructions. These are molecular recognition and self-assembly. The nucleotide bases A and T on two different ss-DNA have affinity towards each other, so do G and C. Effective and stable cis-DNA structures are only formed if the base orders of the individual strands are complementary. Hence, if two complementary single strands of DNA are in a solution, they will eventually recognize each other and hybridize or zip-up forming a cis-DNA. This property of molecular recognition and self-assembly has been exploited in a number of ways to build complex molecular structures [ 114-121]. In the mechanical perspective, if the free energy released by hybridization of two complementary DNA strands is used to lift a hypothetical load, a force capacity of 15 pN can be achieved [122], comparable to that of other molecular machines like kinesin (5 pN) [123],... 

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