VipD of <i>Legionella pneumophila</i> Targets Activated Rab5 and Rab22 to Interfere with Endosomal Trafficking in Macrophages

Ku, Bonsu,Lee, Kwang-Hoon,Park, Wei Sun,Yang, Chul-Su,Ge, Jianning,Lee, Seong-Gyu,Cha, Sun-Shin,Shao, Feng,Heo, Won Do,Jung, Jae U.,Oh, Byung-Ha Public Library of Science 2012 PLoS pathogens Vol.8 No.12

<▼1><P>Upon phagocytosis, <I>Legionella pneumophila</I> translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of <I>L. pneumophila</I> belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of <I>L. pneumophila</I> and delineates the underlying molecular mechanism.</P></▼1><▼2><P><B>Author Summary</B></P><P><I>Legionella pneumophila</I> is a pathogen bacterium that causes Legionnaires' disease accompanied by severe pneumonia. Surprisingly, this pathogen invades and replicates inside macrophages, whose major function is to detect and destroy invading microorganisms. How <I>L. pneumophila</I> can be “immune” to this primary immune cell has been a focus of intensive research. Upon being engulfed by a macrophage cell, <I>L. pneumophila</I> translocates hundreds of bacterial proteins into this host cell. These proteins, called bacterial effectors, are thought to manipulate normal host cellular processes. However, which host molecules and how they are targeted by the bacterial effectors are largely unknown. In this study, we determined the three-dimensional structure of <I>L. pneumophila</I> effector protein VipD, whose function in macrophage was unknown. Ensuing analyses revealed that VipD selectively and tightly binds two host signaling proteins Rab5 and Rab22, which are key regulators of early endosomal vesicle trafficking. These interactions prevent the activated form of Rab5 and Rab22 from binding their downstream signaling proteins, resulting in the blockade of endosomal trafficking in macrophages. The presented work shows that <I>L. pneumophila</I> targets endosomal Rab proteins and delineates the underlying molecular mechanism, providing a new insight into the pathogen's strategies to dysregulate normal intracellular processes.</P></▼2>

Crystal structure of the MukB hinge domain with coiled-coil stretches and its functional implications

Ku, Bonsu,Lim, Jae-Hong,Shin, Ho-Chul,Shin, Seong-Yeol,Oh, Byung-Ha Wiley Subscription Services, Inc., A Wiley Company 2010 Proteins Vol.78 No.6

<P>The structural maintenance of chromosomes (SMC) family proteins are commonly found in the multiprotein complexes involved in chromosome organization, including chromosome condensation and sister chromatid cohesion. These proteins are characterized by forming a V-shaped homo- or heterodimeric structure with two long coiled-coil arms having two ATPase head domains at the distal ends. The hinge domain, located in the middle of the coiled coil, forms the dimer interface. In addition to being the dimerization module, SMC hinges appear to play other roles, including the gateway function for DNA entry into the cohesin complex. Herein, we report the homodimeric structure of the hinge domain of Escherichia coli MukB, which forms a prokaryotic condensin complex with two non-SMC subunits, MukE and MukF. In contrast with SMC hinge of Thermotoga maritima which has a sizable central hole at the dimer interface, MukB hinge forms a constricted dimer interface lacking a hole. Under our assay conditions, MukB hinge does not interact with DNA in accordance with the absence of a notable positively charged surface patch. The function of MukB hinge appears to be limited to dimerization of two copies of MukB molecules. Proteins 2010. © 2009 Wiley-Liss, Inc.</P>

Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68

Ku, Bonsu,Woo, Jae-Sung,Liang, Chengyu,Lee, Kwang-Hoon,Hong, Hyang-Suk,E, Xiaofei,Kim, Key-Sun,Jung, Jae U,Oh, Byung-Ha,Frü,h, Klaus Public Library of Science 2008 PLoS pathogens Vol.4 No.2

<▼1><P>All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine γ-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus.</P></▼1><▼2><P><B>Author Summary</B></P><P><B/></P><P>In higher animals, defective or surplus cells are removed by a process known as apoptosis. On the other hand, defective or damaged cellular components are removed by a process known as autophagy. These two destructive processes are indispensable for the survival and development of an organism. While apoptosis is known as a central host defense mechanism that removes virus-infected cells, the role of autophagy against viral infection has recently emerged. Many viruses express an armory of viral proteins that counteract cell death–mediated innate immune control. One such protein is a homologue of the cellular BCL-2 protein that suppresses apoptosis through inhibitory binding to apoptosis-promoting proteins. Murine γ-herpesvirus 68 also encodes a viral BCL-2, known as M11. In this study, we quantitatively measured the binding affinity of M11 for its potential cellular targets, including ten different proapoptotic proteins and the proautophagic protein Beclin1. We found that M11 neutralizes the proapoptotic proteins broadly rather than selectively to suppress apoptosis. Surprisingly, M11 bound to Beclin1 with the highest affinity, which correlated with its strong antiautophagic activity in cells. These data suggest that M11 suppresses not only apoptosis but also autophagy potently, which ultimately contributes to the viral chronic infection.</P></▼2>

Identification of N-(5-(phenoxymethyl)-1,3,4-thiadiazol-2-yl)acetamide derivatives as novel protein tyrosine phosphatase epsilon inhibitors exhibiting anti-osteoclastic activity

Ku, Bonsu,Yun, Hye-Yeoung,Lee, Kyung Won,Shin, Ho-Chul,Lee, Sang-Rae,Kim, Chang Hyen,Park, Hwangseo,Yi, Kyu Yang,Lee, Chang Hoon,Kim, Seung Jun Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.18

<P><B>Abstract</B></P> <P>Cytosolic protein tyrosine phosphatase epsilon (cyt-PTPε) plays a central role in controlling differentiation and function of osteoclasts, whose overactivation causes osteoporosis. Based on our previous study reporting a number of cyt-PTPε inhibitory chemical compounds, we carried out a further and extended analysis of our compounds to examine their effects on cyt-PTPε-mediated dephosphorylation and on osteoclast organization and differentiation. Among five compounds showing target selectivity to cyt-PTPε over three other phosphatases <I>in vitro</I>, two compounds exhibited an inhibitory effect against the dephosphorylation of cellular Src protein, the cyt-PTPε substrate. Moreover, these two compounds caused destabilization of the podosome structure that is necessary for the bone-resorbing activity of osteoclasts, and also attenuated cellular differentiation of monocytes into osteoclasts, without affecting cell viability. Therefore, these findings not only verified anti-osteoclastic effects of our cyt-PTPε inhibitory compounds, but also showed that cyt-PTPε expressed in osteoclasts could be a putative therapeutic target worth considering.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Sabbath Observance among the Akan`s of Ghana and Its Impact on the Growth of the Seventh-day Adventist Church in Ghana

( Robert Osei Bonsu ) 삼육대학교 선교와사회문제연구소 2013 Asia-Africa Journal of Mission and Ministry(AAMM) Vol.7 No.-

Akan traditional religion is rooted in their custom and traditions. Sabbath rest was an integral part of Akan tradition and custom in antiquity. When the Seventh-day Adventist Church message came to the coast lands of the then Gold Coast, now Ghana, it did not make much impact until it moved to the Ashanti hinterland. The question of interest to this study is, why is the Adventist message still gaining much ground among some Akan tribes in spite of the fact that this tradition of Sabbath rest is no more practiced? Are there certain conceptual commonalities shared by the Akans and the Adventist church with respect to Sabbath observance? What role has the Akan culture played in the history and spread of Adventism in Ghana? The study concludes that Akan traditional religion and Sabbath veneration, one way or the other continue to serve as a catalyst for the spread of Adventism among the indigenes.

John’s Baptism and Christian Baptism: A Comparative Study

( Robert Osei-bonsu ) 삼육대학교 선교와사회문제연구소 2021 Asia-Africa Journal of Mission and Ministry(AAMM) Vol.23 No.-

This study discusses the difference that exists between Christian baptism and John’s baptism. John began his baptism as a precursor of the institution of Christian baptism (John 1:25-26, 33). While some theologians consider John’s baptism as inadequate because it was a baptism of repentance and not of the Holy Spirit, others posit that it was adequate since Apollos was never re-baptized by the Christian community (Acts 18:27, 28; 19:1). Thus, this paper sought to examine the two types of baptism in the New Testament and determine the differences and similarities between the two. From a review of baptism as understood in the Old Testament, and in Qumran and Rabbinic traditions, the paper further discussed baptism in the New Testament. It focused specifically on John’s baptism and Christian baptism as practiced by Christ’s disciples. This study concludes that there is a close relationship between John’s baptism and Christian baptism. Though the two share several similarities, there are also some significant differences. Thus, while John’s baptism locally prepared his people's minds towards Christ’s first coming, Christian baptism universally ushers the believer into the Kingdom of God.

Global Crisis and the Search for a New World Order: A Biblical Response from Daniel 2:41-43

Robert Osei-Bonsu,Samson D,Dakio 삼육대학교 미래사회와기독교연구소 2021 융합학문과 기독교 Vol.2 No.1

The New World Order as a subject and its correlation with global crises is of current interest. Human life has been characterized by intermittent periods of upheavals and relative tranquility. Global crises are specific to each period of history. When crises erupt, there is always a need for a concerted way to resolve them. In modern times, significant crises such as World War I and II have put human existence in a state of hopelessness and meaninglessness. Such catastrophes have compelled world leaders to seek to implement a one-government agenda to assuage humanity s suffering. Attempts to curb such crises have created peace movements and organizations, including the United Nations and the European Union. Despite these intentional efforts to federate nations for a better world, unity and peace seem to remain a mirage. Through an exegetical approach, the study has proven that all attempts to unify nations under the banner of a peaceful global village seem to be bound to failure. Therefore, the study concludes that the past and present sequel of events worldwide agrees with biblical data. The book of Daniel is explicit that a one-world agenda is an illusion.

Graded Absolutism is Still Inadequate: A Response to Norman Geisler

( Robert Osei Bonsu ),( Daniel Dei ) 삼육대학교 선교와사회문제연구소 2015 Asia-Africa Journal of Mission and Ministry(AAMM) Vol.12 No.-

This article examines the Christian ethical concept of graded absolutism with a special attention to its advantages and disadvantages. Advantages of Christian graded absolutism are: it avoids relativism; it successfully answers moral conflicts; and it makes sense of the Cross. The disadvantages of Christian graded absolutism are: difficulty in determining the hierarchy of values in some instances; tendency towards relativism; susceptible to subjectivism; and lack of immediacy towards solving ethical dilemmas. Contrary to Geisler’s positive assessment of Christian graded absolutism, the study concludes that Christian graded absolutism comes close to resolving ethical dilemmas, but it is still inadequate

The Ontology of the Ordained Person: A Theological Evaluation

( Robert Osei Bonsu ),( Samson Dawe Dakio ) 삼육대학교 선교와사회문제연구소 2013 Asia-Africa Journal of Mission and Ministry(AAMM) Vol.8 No.-

Ordination is a significant concept in the history of the Christian Church. The urgency for denominations to formulate a theology of ordination shows that the issue has gone beyond scholarship and becomes a matter crucial to faith. In the absence of a biblical systematic theology of ordination, the quest to know what ordination confers to the ordained person remains problematic. It is in this context that should be understood the functional- ontological dilemma posed by the act of ordination. Through a theological survey, however, this study claims that ordination per se bestows nothing supernatural susceptible to change the ontological make-up of the recipient. Said differently, ordination is a human recognition of the calling of an individual through the laying on of hands that grants more prerogatives and thereby enables the beneficiary to function as an authorized representative of the Church.ABSTRACT-Ordination is a significant concept in the history of the Christian Church. The urgency for denominations to formulate a theology of ordination shows that the issue has gone beyond scholarship and becomes a matter crucial to faith. In the absence of a biblical systematic theology of ordination, the quest to know what ordination confers to the ordained person remains problematic. It is in this context that should be understood the functional- ontological dilemma posed by the act of ordination. Through a theological survey, however, this study claims that ordination per se bestows nothing supernatural susceptible to change the ontological make-up of the recipient. Said differently, ordination is a human recognition of the calling of an individual through the laying on of hands that grants more prerogatives and thereby enables the beneficiary to function as an authorized representative of the Church.

EI/AI 절연코팅된 꼬여진 코일의 인버터서지 및 온도스트레스에 따른 절연수명평가

김본수(Kim BonSu),김한정(Kim HanJung),이정훈(Lee JungHun),이종민(Lee JongMin),이욱기(Lee UkKi),이승열(Lee SeungYoel),김호정(Kim HoJung),조창현(Jo ChangHyun),우명하(Woo MyungHa) 대한전기학회 2017 대한전기학회 학술대회 논문집 Vol.2017 No.10