![]() However, another reason for the difference might be due to the way the role of water is described. The difference between the unbinding forces in the above two studies with implicit and explicit water models may be attributed to the difference in simulation times. The oxygen atoms are shown in red balls, the hydrogen atoms in white, the nitrogen atoms in blue and α carbon atoms in bigger black balls. (b) Definition of the four backbone HBs in the docked β10 region. The neck linker (red) of the leading head is in the undocked state and that of the trailing head is in the docked state. (a) Two motor heads and the neck coiled coil on microtubule. (color online) Structure of kinesin motor domain and the backbone hydrogen bonds of the β10 zipper. In contrast, the backbone HBs at C-terminus of β10 are unstable and can be broken even in the case without an unbinding force.įig. We found that the minimal unbinding force for the N-terminal ASN latch within tens of nanoseconds is 160 pN. In one of our previous studies, we investigated the binding strength of NL with the motor domain by using MD simulations with explicit water model. They used pN force to break the ASN latch in their simulations with implicit water model. However, the backbone HB at the N-terminus of β10, the backbone HB between Asn334 and Gly77 (the ASN latch), is much stronger than other backbone HBs. ![]() performed MD simulations of the undocking process of NL and found that the backbone HBs at the C-terminal part of β10 can be broken easily. In their work on the CNB mechanism of NL docking, Hwang et al. In the docked state, β10 forms four backbone HBs with the motor domain (Fig. The β9 docks to the motor domain through forming a cover-neck bundle (CNB) structure with the N-terminal β0 strand, which has a forward bending tendency. ![]() The first three amino acids dock to the motor domain through forming an extra turn structure, which is the initial step of the NL docking process driven by ATP binding induced motor head rotation and torsion. These three parts of NL dock to the motor domain in three different ways. The NL consists of three parts, including the first three N-terminal amino acids (Lys325, Thr326 and Ile327 in 2KIN ), β9 and β10 (Fig. In kinesin walking cycle, NL undergoes a large conformational change from the undocked state to the docked state repeatedly (Fig. To understand the docking mechanism of β10, it is necessary to find out the origin of the strength difference among these backbone HBs at an amino acid level. These backbone HBs, though they are formed in the same way, show big differences in their effective strength. The C-terminal β10 of NL docks to the motor domain through forming four backbone hydrogen bonds (HBs). The NL consists of amino acids that connect kinesin’s motor domain and coiled-coil stalk. Kinesin’s neck linker (NL) docking to the motor domain is the key force generation step of kinesin. The intimate relationship between the effective strength of protein backbone HB and water revealed here should be considered when performing mechanical analysis for protein conformational changes.Ĭonventional kinesin (kinesin-1, here is referred to as kinesin) is a highly processive motor protein, which effectively converts the chemical energy carried by adenosine triphosphate (ATP) into mechanical force and walks hundreds of steps along a microtubule with cargos. In contrast, the backbone HB at the N-terminus of β10 is protected by the surrounding hydrophobic and hydrophilic residues which cooperate positively with the central backbone HB and make this HB highly strong. Along these channels the water molecules can directly attack the backbone HBs and make these HBs relatively weak. The arrangement of the residues in the C-terminal part of β10 results in the existence of the water-attack channels around the backbone HBs in this region. We find that the strength differences of these backbone HBs mainly arise from their relationships with water molecules which are controlled by arranging the surrounding residue sidechains. Using molecular dynamics method, we investigate the stability of the backbone HBs in explicit water environment. The origins of these strength differences are still unclear. These backbone hydrogen bonds show big differences in their effective strength. In this process, NL’s β10 portion forms four backbone hydrogen bonds (HBs) with the motor domain. Docking of the kinesin’s neck linker (NL) to the motor domain is the key force-generation process of the kinesin.
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