KINESIN AND DYNEIN SMART NANOMOTORS: TOWARDS BIO-NANOROBOTIC SYSTEMS

H. R. KHATAEE,A. R. KHATAEE 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2010 NANO Vol.5 No.1

The majority of active transport in cells is driven by two classes of intelligent nanomotors, kinesin and dynein. The intelligence of kinesin and dynein nanomotors is the key toward developing intelligent bio-nanosystems for various nanotechnological applications. The first step in this regard is the ability to determine the structure, behavior, and properties of basic bio-nanocomponents, such as proteins. Therefore, in this paper we have described structures and mechanisms of kinesin and dynein protein nanomotors. Kinesin and dynein nanomotors are multi-protein complexes which are responsible for various dynamical processes for transporting single molecules over small distances to cell movement and growth. They convert the chemical energy into mechanical work directly rather than via an intermediate energy. Kinesin and dynein protein nanomotors are self-guiding systems. They have evolved to enable movement on their polymer filaments, either on cellular or supra-cellular levels, to recognize the direction of movement. Kinesin and dynein nanomotors have different properties, but in the cell they are known to cooperate and even to compete with each others during their function. It has been indicated that kinesin and dynein nanomotors can be defined as ideal bio-nanocomponents for bio-nanorobotic systems because of their small size, perfect structure, smart and high efficiency.

N-Acetyl-D-Glucosamine Kinase Interacts with Dynein-Lis1-NudE1 Complex and Regulates Cell Division

Sharif, Syeda Ridita,Islam, Md. Ariful,Moon, Il Soo Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.9

N-acetyl-D-glucosamine kinase (GlcNAc kinase or NAGK) primarily catalyzes phosphoryl transfer to GlcNAc during amino sugar metabolism. Recently, it was shown NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and upregulates axo-dendritic growth, which is an enzyme activity-independent, non-canonical structural role. The authors examined the distributions of NAGK and NAGK-dynein complexes during the cell cycle in HEK293T cells. NAGK was expressed throughout different stages of cell division and immunocytochemistry (ICC) showed NAGK was localized at nuclear envelope, spindle microtubules (MTs), and kinetochores (KTs). A proximity ligation assay (PLA) for NAGK and DYNLRB1 revealed NAGK-dynein complex on nuclear envelopes in prophase cells and on chromosomes in metaphase cells. NAGK-DYNLRB1 PLA followed by Lis1/NudE1 immunostaining showed NAGK-dynein complexes were colocalized with Lis1 and NudE1 signals, and PLA for NAGK-Lis1 showed similar signal patterns, suggesting a functional link between NAGK and dynein-Lis1 complex. Subsequently, NAGK-dynein complexes were found in KTs and on nuclear membranes where KTs were marked with CENP-B ICC and nuclear membrane with lamin ICC. Furthermore, knockdown of NAGK by small hairpin (sh) RNA was found to delay cell division. These results indicate that the NAGK-dynein interaction with the involvements of Lis1 and NudE1 plays an important role in prophase nuclear envelope breakdown (NEB) and metaphase MT-KT attachment during eukaryotic cell division.

N-Acetyl-D-Glucosamine Kinase Interacts with Dynein-Lis1-NudE1 Complex and Regulates Cell Division

Il Soo Moon,Syeda Ridita Sharif,Md. Ariful Islam 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.9

N-acetyl-D-glucosamine kinase (GlcNAc kinase or NAGK) primarily catalyzes phosphoryl transfer to GlcNAc during amino sugar metabolism. Recently, it was shown NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and upregulates axo-dendritic growth, which is an enzyme activity-independent, non-canonical struc-tural role. The authors examined the distributions of NAGK and NAGK-dynein complexes during the cell cycle in HEK293T cells. NAGK was expressed throughout different stages of cell division and immunocytochemistry (ICC) showed NAGK was localized at nuclear envelope, spindle microtubules (MTs), and kinetochores (KTs). A proximity ligation assay (PLA) for NAGK and DYNLRB1 revealed NAGK-dynein complex on nuclear envelopes in prophase cells and on chromosomes in metaphase cells. NAGK-DYNLRB1 PLA followed by Lis1/NudE1 immunostaining showed NAGK-dynein complexes were colocalized with Lis1 and NudE1 signals, and PLA for NAGK-Lis1 showed similar signal patterns, suggesting a functional link between NAGK and dynein-Lis1 complex. Subsequently, NAGK-dynein complexes were found in KTs and on nuclear membranes where KTs were marked with CENP-B ICC and nuclear membrane with lamin ICC. Furthermore, knockdown of NAGK by small hairpin (sh) RNA was found to delay cell division. These results indicate that the NAGK-dynein interaction with the involvements of Lis1 and NudE1 plays an important role in prophase nuclear envelope breakdown (NEB) and metaphase MT-KT attachment during eukaryotic cell division.

Nucleotide-dependent control of internal strains in ring-shaped AAA+ motors.

Hwang, Wonmuk,Lang, Matthew J SPRINGER SCIENCE + BUSINESS MEDIA 2013 Cellular and molecular bioengineering Vol.6 No.1

<P>The AAA+ (ATPase Associated with various cellular Activities) machinery represents an extremely successful and widely used design plan for biological motors. Recently found crystal structures are beginning to reveal nucleotide-dependent conformational changes in the canonical hexameric rings of the AAA+ motors. However, the physical mechanism by which ATP binding on one subunit allosterically propagates across the entire ring remains to be found. Here we analyze and compare structural organization of three ring-shaped AAA+ motors, ClpX, HslU, and dynein. By constructing multimers using subunits of identical conformations, we find that individual subunits locally possess helical geometries with varying pitch, radius, chirality, and symmetry number. These results suggest that binding of an ATP to a subunit imposes conformational constraint that must be accommodated by more flexible nucleotide-free subunits to relieve mechanical strain on the ring. Local deformation of the ring contour and subsequent propagation of strains may be a general strategy that AAA+ motors adopt to generate force while achieving functional diversity.</P>

Atomistic analysis of ATP hydrolysis effect on a dynein walking mechanism

조수진,Min Hyeok Kim,JAE-BOONG CHOI,Moon-Ki Kim 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.7

Dynein is a microtubule motor protein that is highly involved in cell motility. Although its atomic structure was recently reported, it has been believed that dynein, like other motor proteins, generates a large swing motion powered by ATP hydrolysis. In this paper, we have analyzed ATP hydrolysis effect on the walking mechanism of dynein at the atomic level using a C α coarse-grained elastic network model. Normal mode analysis (NMA) revealed that the detachment of the linker from the head of dynein, which is triggered by ATP hydrolysis, facilitates the main swing motion of dynein in two ways: allowing the bending motion as an extra degree-of-freedom (topologically) and lowering the energy barrier between the closed and open forms (energetically). This large conformational transition pathway is successfully generated by Elastic network interpolation (ENI). Comparison between the ENI pathway and the NMA results clearly elucidates the role of ATP hydrolysis in motor proteins as well as the swing motion of dynein in atomic detail.

N-Acetyl-D-Glucosamine Kinase Promotes the Axonal Growth of Developing Neurons

Islam, Md. Ariful,Sharif, Syeda Ridita,Lee, HyunSook,Moon, Il Soo Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.10

N-acetyl-D-glucosamine kinase (NAGK) plays an enzyme activity-independent, non-canonical role in the dendritogenesis of hippocampal neurons in culture. In this study, we investigated its role in axonal development. We found NAGK was distributed throughout neurons until developmental stage 3 (axonal outgrowth), and that its axonal expression remarkably decreased during stage 4 (dendritic outgrowth) and became negligible in stage 5 (mature). Immunocytochemistry (ICC) showed colocalization of NAGK with tubulin in hippocampal neurons and with Golgi in somata, dendrites, and nascent axons. A proximity ligation assay (PLA) for NAGK and Golgi marker protein followed by ICC for tubulin or dynein light chain roadblock type 1 (DYNLRB1) in stage 3 neurons showed NAGK-Golgi complex colocalized with DYNLRB1 at the tips of microtubule (MT) fibers in axonal growth cones and in somatodendritic areas. PLAs for NAGK-dynein combined with tubulin or Golgi ICC showed similar signal patterns, indicating a three way interaction between NAGK, dynein, and Golgi in growing axons. In addition, overexpression of the NAGK gene and of kinase mutant NAGK genes increased axonal lengths, and knockdown of NAGK by small hairpin (sh) RNA reduced axonal lengths; suggesting a structural role for NAGK in axonal growth. Finally, transfection of 'DYNLRB1 (74-96)', a small peptide derived from DYNLRB1's C-terminal, which binds with NAGK, resulted in neurons with shorter axons in culture. The authors suggest a NAGK-dynein-Golgi tripartite interaction in growing axons is instrumental during early axonal development.

N-Acetyl-D-Glucosamine Kinase Promotes the Axonal Growth of Developing Neurons

Md. Ariful Islam,문일수,Syeda Ridita Sharif,이현숙 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.10

N-acetyl-D-glucosamine kinase (NAGK) plays an enzyme activity-independent, non-canonical role in the dendritogenesis of hippocampal neurons in culture. In this study, we investigated its role in axonal development. We found NAGK was distributed throughout neurons until developmental stage 3 (axonal outgrowth), and that its axonal expression remarkably decreased during stage 4 (dendritic outgrowth) and became negligible in stage 5 (mature). Immunocytochemistry (ICC) showed colocalization of NAGK with tubulin in hippocampal neurons and with Golgi in somata, dendrites, and nascent axons. A proximity ligation assay (PLA) for NAGK and Golgi marker protein followed by ICC for tubulin or dynein light chain roadblock type 1 (DYNLRB1) in stage 3 neurons showed NAGK-Golgi complex colocalized with DYNLRB1 at the tips of microtubule (MT) fibers in axonal growth cones and in somatodendritic areas. PLAs for NAGK-dynein combined with tubulin or Golgi ICC showed similar signal patterns, indicating a three way interaction between NAGK, dynein, and Golgi in growing axons. In addition, overexpression of the NAGK gene and of kinase mutant NAGK genes increased axonal lengths, and knockdown of NAGK by small hairpin (sh) RNA reduced axonal lengths; suggesting a structural role for NAGK in axonal growth. Finally, transfection of ‘DYNLRB1 (74-96)’, a small peptide derived from DYNLRB1’s C-terminal, which binds with NAGK, resulted in neurons with shorter axons in culture. The authors suggest a NAGK-dynein-Golgi tripartite interaction in growing axons is instrumental during early axonal development.

Novel DNAH1 Mutation Loci Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Literature Review

Zhuang Bao-Jun,Xu Su-Yun,Dong Liang,Zhang Pei-Hai,Zhuang Bao-Lin,Huang Xiao-Peng,Li Guang-Sen,You Yao-Dong,Chen Di'Ang,Yu Xu-Jun,Chang De-Gui 대한남성과학회 2022 The World Journal of Men's Health Vol.40 No.4

The protein encoded by dynein axonemal heavy chain 1 (DNAH1) is a part of dynein, which regulates the function of cilia and sperm flagella. The mutant of DNAH1 causes the deletion of inner dynein arm 3 in the flagellum, leading to multiple morphological abnormalities of the sperm flagella (MMAF) and severe asthenozoospermia. However, instead of asthenozoospermia and MMAF, the result caused by the mutation of DNAH1 remains unknown. Here we report a male infertility patient with severe asthenozoospermia and teratozoospermia. We found two heterozygous mutations in DNAH1 (c.6912C>A and c.7076G>T) and which were reported to be associated with MMAF for the first time. We next collected and analyzed 65 cases of DNAH1 mutation and found that the proportion of short flagella is the largest, while the bent flagella account for the smallest, and the incidence of head deformity is not high in the sperm of these patients. Finally, we also analyzed 31 DNAH1 mutation patients who were treated with intracytoplasmic sperm injection (ICSI) and achieved beneficial outcomes. We hope our research will be helpful in the diagnosis and treatment of male infertility caused by DNAH1 mutation.

전자현미경상 Dynein Inner Arms의 결손을 보인 Immotile Cilia Syndrome 1례

강성길 ( Sung Kil Kang ),최현 ( Hyun Choi ),김달현 ( Dal Hyun Kim ),임대현 ( Dae Hyun Lim ),김정희 ( Jung Hee Kim ),손병관 ( Byong Kwan Son ),한혜승 ( Hye Seung Han ) 대한소아알레르기호흡기학회 2002 소아알레르기 및 호흡기학회지 Vol.12 No.1

NMR Characterization of Oxidized Form of Human 8-kDa Dynein Light Chain

지승욱,신재선,정우진 한국자기공명학회 2010 Journal of the Korean Magnetic Resonance Society Vol.14 No.2

Redox-dependent conformational change of human 8-kDa Dynein light chain (LC8) plays important role in regulating NF-κB signaling pathway. In this study we characterized the structural states of the oxidized and reduced forms of LC8 by using NMR spectroscopy. The 1H-15N 2D HSQC spectra of oxidized LC8 indicated that no significant change in tertiary structure of LC8 occurred upon oxidation. The chemical shift perturbations of LC8 upon oxidation suggest a redox-dependent quaternary structural change.