• Title/Summary/Keyword: PreSMo

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Rescuing p53 from mdm2 by a pre-structured motif in intrinsically unfolded SUMO specific protease 4

  • Kim, Do-Hyoung;Lee, Chewook;Kim, Bom;Lee, Si-Hyung;Han, Kyou-Hoon
    • BMB Reports
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    • v.50 no.10
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    • pp.485-486
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    • 2017
  • Many intrinsically unstructured/unfolded proteins (IUPs) contain transient local secondary structures even though they are "unstructured" in a tertiary sense. These local secondary structures are named "pre-structured motifs (PreSMos)" and in fact are the specificity determinants for IUP-target binding, i.e., the active sites in IUPs. Using high-resolution NMR we have delineated a PreSMo active site in the intrinsically unfolded mid-domain (residues 201-300) of SUMO-specific protease 4 (SUSP4). This 29-residue motif which we termed a p53 rescue motif can protect p53 from mdm2 quenching by binding to the p53-helix binding pocket in mdm2(3-109). Our work demonstrates that the PreSMo approach is quite effective in providing a structural rationale for interactions of p53-mdm2-SUSP4 and opens a novel avenue for designing mdm2-inhibiting anticancer compounds.

PreSMo Target-Binding Signatures in Intrinsically Disordered Proteins

  • Kim, Do-Hyoung;Han, Kyou-Hoon
    • Molecules and Cells
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    • v.41 no.10
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    • pp.889-899
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    • 2018
  • Intrinsically disordered proteins (IDPs) are highly unorthodox proteins that do not form three-dimensional structures under physiological conditions. The discovery of IDPs has destroyed the classical structure-function paradigm in protein science, 3-D structure = function, because IDPs even without well-folded 3-D structures are still capable of performing important biological functions and furthermore are associated with fatal diseases such as cancers, neurodegenerative diseases and viral pandemics. Pre-structured motifs (PreSMos) refer to transient local secondary structural elements present in the target-unbound state of IDPs. During the last two decades PreSMos have been steadily acknowledged as the critical determinants for target binding in dozens of IDPs. To date, the PreSMo concept provides the most convincing structural rationale explaining the IDP-target binding behavior at an atomic resolution. Here we present a brief developmental history of PreSMos and describe their common characteristics. We also provide a list of newly discovered PreSMos along with their functional relevance.

Board Level Reliability Evaluation for Package on Package

  • Hwang, Tae-Gyeong;Chung, Ji-Young
    • Proceedings of the International Microelectronics And Packaging Society Conference
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    • 2007.04a
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    • pp.37-47
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    • 2007
  • Factor : Structure Metal pad & SMO size Board level TC test : - Large SMO size better Board level Drop test : - Large SMO size better Factor : Structure Substrate thickness Board level TC test : - Thick substrate better Board level Drop test : - Substrate thickness is not a significant factor for drop test Factor : Material Solder alloy Board level TC test : - Not so big differences over Pb-free solder and NiAu, OSP finish Board level Drop test : - Ni/Au+SAC105, CuOSP+LF35 are better Factor : Material Pad finish Board level TC test : - NiAu/NiAu is best Board livel Drop test : - CuOSP is best Factor : Material Underfill Board level TC test - Several underfills (reworkable) are passed TCG x500 cycles Board level Drop test : - Underfill lots have better performance than non-underfill lots Factor : Process Multiple reflow Board level TC test : - Multiple reflow is not a significant actor for TC test Board level Drop test : N/A Factor : Process Peak temp Board level TC test : - Higher peak temperature is worse than STD Board level Drop test : N/A Factor : Process Stack method Board level TC test : - No big difference between pre-stack and SMT stack Board level Drop test : - Flux dipping is better than paste dipping but failure rate is more faster

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An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor

  • Kim, Do-Hyoung;Wright, Anthony;Han, Kyou-Hoon
    • BMB Reports
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    • v.50 no.10
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    • pp.522-527
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    • 2017
  • A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity. We carried out heteronuclear multi-dimensional NMR experiments on hGR tau1c in a more physiological aqueous buffer solution and found that it forms three helices that are ~30% pre-populated. Since pre-populated helices in several TADs were shown to be key elements for transcriptional activity, the three pre-formed helices in hGR tau1c delineated in this study should be critical determinants of the transcriptional activity of hGR. The presence of pre-structured helices in hGR tau1c strongly suggests that the existence of pre-structured motifs in target-unbound TADs is a very broad phenomenon.

Structural investigation on the intrinsically disordered N-terminal region of HPV16 E7 protein

  • Lee, Chewook;Kim, Do-Hyoung;Lee, Si-Hyung;Su, Jiulong;Han, Kyou-Hoon
    • BMB Reports
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    • v.49 no.8
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    • pp.431-436
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    • 2016
  • Human papillomavirus (HPV) is the major cause of cervical cancer, a deadly threat to millions of females. The early oncogene product (E7) of the high-risk HPV16 is the primary agent associated with HPV-related cervical cancers. In order to understand how E7 contributes to the transforming activity, we investigated the structural features of the flexible N-terminal region (46 residues) of E7 by carrying out N-15 heteronuclear NMR experiments and replica exchange molecular dynamics simulations. Several NMR parameters as well as simulation ensemble structures indicate that this intrinsically disordered region of E7 contains two transient (10-20% populated) helical pre-structured motifs that overlap with important target binding moieties such as an E2F-mimic motif and a pRb-binding LXCXE segment. Presence of such target-binding motifs in HPV16 E7 provides a reasonable explanation for its promiscuous target-binding behavior associated with its transforming activity.

Integrated Sliding-Mode Sensorless Driver with Pre-driver and Current Sensing Circuit for Accurate Speed Control of PMSM

  • Heo, Sewan;Oh, Jimin;Kim, Minki;Suk, Jung-Hee;Yang, Yil Suk;Park, Ki-Tae;Kim, Jinsung
    • ETRI Journal
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    • v.37 no.6
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    • pp.1154-1164
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    • 2015
  • This paper proposes a fully sensorless driver for a permanent magnet synchronous motor (PMSM) integrated with a digital motor controller and an analog pre-driver, including sensing circuits and estimators. In the motor controller, a position estimator estimates the back electromotive force and rotor position using a sliding-mode observer. In the pre-driver, drivers for the power devices are designed with a level shifter and isolation technique. In addition, a current sensing circuit measures a three-phase current. All of these circuits are integrated in a single chip such that the driver achieves control of the speed with high accuracy. Using an IC fabricated using a $0.18{\mu}m$ BCDMOS process, the performance was verified experimentally. The driver showed stable operation in spite of the variation in speed and load, a similar efficiency near 1% compared to a commercial driver, a low speed error of about 0.1%, and therefore good performance for the PMSM drive.

Wide-line NMR and DSC studies on intrinsically disordered p53 transactivation domain and its helically pre-structured segment

  • Tompa, Peter;Han, Kyou-Hoon;Bokor, Monika;Kamasa, Pawel;Tantos, Agnes;Fritz, Beata;Kim, Do-Hyoung;Lee, Chewook;Verebelyi, Tamas;Tompa, Kalman
    • BMB Reports
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    • v.49 no.9
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    • pp.497-501
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    • 2016
  • Wide-line 1H NMR intensity and differential scanning calorimetry measurements were carried out on the intrinsically disordered 73-residue full transactivation domain (TAD) of the p53 tumor suppressor protein and two peptides: one a wild type p53 TAD peptide with a helix pre-structuring property, and a mutant peptide with a disabled helix-forming propensity. Measurements were carried out in order to characterize their water and ion binding characteristics. By quantifying the number of hydrate water molecules, we provide a microscopic description for the interactions of water with a wild-type p53 TAD and two p53 TAD peptides. The results provide direct evidence that intrinsically disordered proteins (IDPs) and a less structured peptide not only have a higher hydration capacity than globular proteins, but are also able to bind a larger amount of charged solute ions.