• Title/Summary/Keyword: functional domain

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Functional Role of a Conserved Sequence Motif in the Oxygen-dependent Degradation Domain of Hypoxia-inducible Factor 1α in the Recognition of p53

  • Chi, Seung-Wook
    • Genomics & Informatics
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    • v.6 no.2
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    • pp.72-76
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    • 2008
  • Hypoxia-inducible factor $1{\alpha}\;(HIF1{\alpha})$ is a transcription factor that plays a key role in the adaptation of cells to low oxygen stress and oxygen homeostasis. The oxygen-dependent degradation (ODD) domain of $HIF1{\alpha}$ is responsible for the negative regulation of $HIF1{\alpha}$ in normoxia. The interactions of the $HIF1{\alpha}$ ODD domain with partner proteins such as von Hippel-Lindau tumor suppressor (pVHL) and p53 are mediated by two sequence motifs, the N- and C-terminal ODD(NODD and CODD). Multiple sequence alignment with $HIF1{\alpha}$ homologs from human, monkey, pig, rat, mouse, chicken, frog, and zebrafish has demonstrated that the NODD and CODD motifs have noticeably high conservation of the primary sequence across different species and isoforms. In this study, we carried out molecular dynamics simulation of the structure of the $HIF1{\alpha}$ CODD motif in complex with the p53 DNA-binding domain (DBD). The structure reveals specific functional roles of highly conserved residues in the CODD sequence motif of $HIF1{\alpha}$ for the recognition of p53.

Engineering Hybrid Proteins by Modular Recombination and Evolutionary Optimization (모듈성 단백질의 재설계 및 개량)

  • Lee, Seung-Goo;Rha, Eu-Gene;Ha, Jae-Seok;Lee, Jeong-Min;Kim, Sun-Hwa
    • Microbiology and Biotechnology Letters
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    • v.36 no.2
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    • pp.149-157
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    • 2008
  • Many proteins consist of distinctive domains that can act independently or cooperatively to achieve a unique function. As these domains evolve from a naturally existing repertoire of functional domains, this implies that domain organization is an intrinsic element involved in building the complex structure and function of proteins. Thus, identifying functional domains would appear to be critical to the elucidation of questions related to protein evolution, folding, and the engineering of hybrid proteins for tai- lored applications. However, the simple application of "Lego-like assembly" to the engineering of hybrid proteins is an oversimplification, as many hybrid constructs lack structural stability, usually due to unfavorable domain contacts. Thus, directed evolution, along with computational studies, may help to engineer hybrid proteins with improved physico-chemical properties. Accordingly, this paper introduces several approaches to functional hybrid protein engineering that potentially can be used to create modulators of gene transcription and cell signaling, and novel biosensors to analyze biological functions in vivo.

Cytosolic domain regulates the calcium sensitivity and surface expression of BEST1 channels in the HEK293 cells

  • Kwon Woo Kim;Junmo Hwang;Dong-Hyun Kim;Hyungju Park;Hyun-Ho Lim
    • BMB Reports
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    • v.56 no.3
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    • pp.172-177
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    • 2023
  • BEST family is a class of Ca2+-activated Cl- channels evolutionary well conserved from bacteria to human. The human BEST paralogs (BEST1-BEST4) share significant amino acid sequence homology in the N-terminal region, which forms the transmembrane helicases and contains the direct calcium-binding site, Ca2+-clasp. But the cytosolic C-terminal region is less conserved in the paralogs. Interestingly, this domain-specific sequence conservation is also found in the BEST1 orthologs. However, the functional role of the C-terminal region in the BEST channels is still poorly understood. Thus, we aimed to understand the functional role of the C-terminal region in the human and mouse BEST1 channels by using electrophysiological recordings. We found that the calcium-dependent activation of BEST1 channels can be modulated by the C-terminal region. The C-terminal deletion hBEST1 reduced the Ca2+-dependent current activation and the hBEST1-mBEST1 chimera showed a significantly reduced calcium sensitivity to hBEST1 in the HEK293 cells. And the C-terminal domain could regulate cellular expression and plasma membrane targeting of BEST1 channels. Our results can provide a basis for understanding the C-terminal roles in the structure-function of BEST family proteins.

Identification of Conserved Protein Domain Combination based on Association Rule (연관성 규칙에 기반한 보존된 단백질 도베인 조합의 식별)

  • Jung, Suk-Hoon;Jang, Woo-Hyuk;Han, Dong-Soo
    • Journal of KIISE:Computing Practices and Letters
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    • v.15 no.5
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    • pp.375-379
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    • 2009
  • Protein domain is the conserved unit of compact tree-dimensional structure and evolution, which carries specific function. Domains may appear in patterns in proteins, since they have been conserved through the evolution for functional formation of proteins. In this paper, we propose a formulated method for conservation analysis of domain combination based on association rule. Proposed method measures mutual dependency of domains in a combination, as well as co-occurrence frequency of them, which is conventionally used. Based on the method, we extracted conserve domain combinations in S.cerevisiae proteins and analyzed their functions based on Gene Ontology. From the results, we drew conclusions that domains in S.cerevisiae proteins form patterns whose members are highly affiliated to one another, and that extracted patterns tend to be associated with molecular function. Moreover, the results testified to proposed method superior to conventional ones for identifying domain combinations conserved for functional cooperation.

Analysis of the functional domains of CFTase gene cloned from Xanthomonas oryzae #5 using recombinant deletion mutant

  • Kim, Byeong-U;Yu, Dong-Ju;Ryu, Hye-Gyeong;Park, Ju-Hui
    • 한국생물공학회:학술대회논문집
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    • 2001.11a
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    • pp.727-730
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    • 2001
  • Various recombinant deletion mutants were constructed from cycloinulo - oligosaccharide fructanotransferase(CFTase) gene of Xanthomonas oryzae #5 . The mutants were expressed in Escherichia coli DH5${\alpha}$. We were able to obtain three recombinant proteins were purified, and examine their CFTase and hydrolyzing activity. N-terminal deletion mutant had both CFTase activity and hydrolyzing activity. however, in C-terminal and N,C-terminal deletion mutant disappeared CFTase activity, but hydrolyzing activity remained. From there results, it seems that the C-terminal region(amino acid $1173{\sim}1333$) is important for cyclization.

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Nonlinear hierarchical motion estimation method based on decompositionof the functional domain (범함수 정의역 분할에 바탕을 둔 비선형 계층적 움직임 추정기법)

  • 심동규;박래홍
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.21 no.4
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    • pp.807-821
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    • 1996
  • In this paper, we proposed a nonlinear hierarchical mtion estimation method. Generally, the conventional hierarchical motion estimation methods have been proposed for fast convergence and detection of large motions. But they have a common drawback that large error in motion estimation is propapated across motion discontinuities. This artifiact is due to the constriaint of motion continuity and the linear interpolation of motion vectors between hierarchical levels. In this paper, we propose an effective hierarchical motion estimation mechod that is robust to motion discontinuities. The proposed algorithm is based on the decomposition of the functional domain for optimizing the intra-level motion estimation functional. Also, we propose an inter-level nonlinear motion estimation equation rather than using the conventional linearprojection scheme of motion field. computer simulations with several test sequences show tht the proposed algorithm performs better than several conventional methods.

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A hybrid inverse method for small scale parameter estimation of FG nanobeams

  • Darabi, A.;Vosoughi, Ali R.
    • Steel and Composite Structures
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    • v.20 no.5
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    • pp.1119-1131
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    • 2016
  • As a first attempt, an inverse hybrid numerical method for small scale parameter estimation of functionally graded (FG) nanobeams using measured frequencies is presented. The governing equations are obtained with the Eringen's nonlocal elasticity assumptions and the first-order shear deformation theory (FSDT). The equations are discretized by using the differential quadrature method (DQM). The discretized equations are transferred from temporal domain to frequency domain and frequencies of the nanobeam are obtained. By applying random error to these frequencies, measured frequencies are generated. The measured frequencies are considered as input data and inversely, the small scale parameter of the beam is obtained by minimizing a defined functional. The functional is defined as root mean square error between the measured frequencies and calculated frequencies by the DQM. Then, the conjugate gradient (CG) optimization method is employed to minimize the functional and the small scale parameter is obtained. Efficiency, convergence and accuracy of the presented hybrid method for small scale parameter estimation of the beams for different applied random error, boundary conditions, length-to-thickness ratio and volume fraction coefficients are demonstrated.

ASYMPTOTIC BEHAVIORS OF ALTERNATIVE JENSEN FUNCTIONAL EQUATIONS-REVISITED

  • Chung, Jaeyoung;Choi, Chang-Kwon
    • The Pure and Applied Mathematics
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    • v.19 no.4
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    • pp.409-421
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    • 2012
  • In this paper, using an efficient change of variables we refine the Hyers-Ulam stability of the alternative Jensen functional equations of J. M. Rassias and M. J. Rassias and obtain much better bounds and remove some unnecessary conditions imposed in the previous result. Also, viewing the fundamentals of what our method works, we establish an abstract version of the result and consider the functional equations defined in restricted domains of a group and prove their stabilities.

ON THE STABILITY OF A CUBIC FUNCTIONAL EQUATION

  • Jun, Kil-Woung;Lee, Yang-Hi
    • Journal of the Chungcheong Mathematical Society
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    • v.21 no.3
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    • pp.377-384
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    • 2008
  • In this paper, we prove the stability of the functional equation $$\sum\limits_{i=0}^{3}3Ci(-1)^{3-i}f(ix+y)-3!f(x)=0$$ in the sense of P. $G{\breve{a}}vruta$ on the punctured domain. Also, we investigate the superstability of the functional equation.

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