• Title/Summary/Keyword: transmembrane protein

Search Result 284, Processing Time 0.029 seconds

Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

  • Kanai, Yoshikatsu;Endou, Hitoshi
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.8 no.3
    • /
    • pp.117-127
    • /
    • 2004
  • The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

CMTM5-v1, a four-transmembrane protein, presents a secreted form released via a vesicle-mediated secretory pathway

  • Li, Henan;Guo, Xiaohuan;Shao, Luning;Plate, Markus;Mo, Xiaoning;Wang, Yu;Han, Wenling
    • BMB Reports
    • /
    • v.43 no.3
    • /
    • pp.182-187
    • /
    • 2010
  • family (CMTM) is a novel family of proteins linking classical chemokines and the transmembrane 4 superfamily (TM4SF). Our earlier studies indicated several CMTM members (such as CKLF1 and CMTM2) have a secreted form. This is the first report of the secreted form of CMTM5-v1, the major RNA splicing form of CMTM5, which is produced as small vesicles (<100 nm diameter) and floats at a peak density of 1.19 g/ml on continuous sucrose gradients. CMTM5-v1 has no obvious co-localization with CD63 or Golgi complex. In addition, brefeldin A but not wortmannin can inhibit the secretion of CMTM5-v1. Our results suggest that CMTM5-v1 might be secreted via a different vesicle-mediated secretory pathway, which will be helpful for the studies of vesicle-mediated secretion and MARVEL domain-containing proteins.

The first insight into the structure of the Photosystem II reaction centre complex at $6{\AA}$ resolution determined by electron crystallography

  • Rhee, Kyong-Hi
    • Proceedings of the Botanical Society of Korea Conference
    • /
    • 1999.08a
    • /
    • pp.83-90
    • /
    • 1999
  • Electron crystallography of two-dimensional crystalsand electron cryo-microscopy is becoming an established method for determining the structure and function of a variety of membrane proteins that are providing difficult to crystallize in three dimension. In this study this technique has been used to investigate the structure of a ~160 kDa reaction centre sub-core complex of photosystem II. Photosystem II is a photosynthetic membrane protein consisting of more than 25 subunits. It uses solar energy to split water releasing molecular oxygen into the atmosphere and creates electrochemical potential across the thylakoid membrane, which is eventually utilized to generate ATP and NADPH. Images were taken using Philips CM200 field emission gun electron microscope with an acceleration voltage of 200kW at liquid nitrogen temperature. In total, 79 images recorded dat tilt angles ranging from 0 to 67 degree yielded amplitudes and phases for a three-dimensional map with an in-plant resolution of 6$\AA$ and 11.4$\AA$ in the third dimension shows at least 23 transmembrane helices resolved in a monomeric complex, of which 18 were able to be assigned to the D1, D2, CP47 , and cytochrome b559 alfa beta-subunits with their associated pigments that ae active in electron transport (Rhee, 1998, Ph.D.thesis). The D1/D2 heterodimer is located in the central position within the complex and its helical scalffold is remarkably similar to that of the reaction centres not only in purple bacteria but also in plant photosystem I (PSI) , indicating a common evoluationary origin of all types of reaction centre in photosynthetic organism known today 9RHee et al. 1998). The structural homology is now extended to the inner antenna subunit, ascribed to CP47 in our map, where the 6 transmembrane helices show a striking structural similarity to the corresponding helices of the PSI reaction centre proteins. The overall arrangement of the chlorophylls in the D1 /D2 heterodimer, and in particular the distance between the central pair, is ocnsistent with the weak exciton coupling of P680 that distinguishes this reaction centre from bacterial counterpart. The map in most progress towards high resolution structure will be presented and discussed.

  • PDF

Protection of rainbow trout (Oncorhynchus mykiss) against infectious hematopoietic necrosis virus (IHNV) by immunization with G gene's cytoplasmic and transmembrane region-deleted single-cycle IHNV

  • Jae Young, Kim;Jun Soung, Kwak;Hyoung Jun, Kim;Ki Hong, Kim
    • Journal of fish pathology
    • /
    • v.35 no.2
    • /
    • pp.157-165
    • /
    • 2022
  • Single-cycle viruses generated by reverse genetic technology are replication-incompetent viruses due to the elimination of gene(s) essential for viral replication, which provides a way to overcome the safety problem in attenuated viruses. Infectious hematopoietic necrosis virus (IHNV) is a major pathogen causing severe damage in cultured salmonid species. In the present study, we generated a single-cycle IHNV lacking the transmembrane and cytoplasmic domain in the G gene (rIHNV-GΔTM) and evaluated the prophylactic potential of rIHNV-GΔTM in rainbow trout (Oncorhynchus mykiss). To produce rIHNV-GΔTM, IHNV G protein-expressing Epithelioma papulosum cyprini (EPC) cells were established. However, as the efficiency of rIHNV-GΔTM production in EPC cell clones was not high, fish were immunized with a low-tittered single-cycle virus (1.5 × 102 PFU/fish). Despite the low dose, the single-cycle IHNV induced significant protection in rainbow trout against IHNV infection, suggesting high immunogenicity of rIHNV-GΔTM. No significant difference in serum ELISA titers against IHNV between the rIHNV-GΔTM immunized group and the control group suggests that the immunized dose of rIHNV-GΔTM might be too low to induce significant humoral adaptive immune responses in rainbow trout. The involvement of adaptive cellular immunity or innate immunity in the present significantly higher protection by the immunization with rIHNV-GΔTM should be further investigated to know the protection mechanism.

Aluminium increase Iron uptake into Glial cells

  • Cheong, Jae-Hoon;Lim, Sung-Sup;Lee, Choong-Jae
    • Proceedings of the PSK Conference
    • /
    • 2002.10a
    • /
    • pp.293.3-294
    • /
    • 2002
  • In the brain, glial cells serve in the role to sequester metal from the neural microenvironment and therefore play an important role as a cellular deposition site. The central nervous system is highly vulnerable to oxidative stress, and free iron can stimulate oxidative stress by the Fenton reaction. Aluminum may upregulates the transferrin-independent iron uptake system and stimulate oxidative stress. Nramp2. also known as DMT 1. is a 12-transmembrane(TM) domain protein responsible for dietary iron uptake as well as metal ions such as iron. lead, mangamese. zinc. copper, and cobait. (omitted)

  • PDF

Paroxysmal kinesigenic dyskinesia in a patient with a PRRT2 mutation and centrotemporal spike discharges on electroencephalogram: case report of a 10-year-old girl

  • Seo, Sun Young;You, Su Jeong
    • Clinical and Experimental Pediatrics
    • /
    • v.59 no.sup1
    • /
    • pp.157-160
    • /
    • 2016
  • Coexistence of paroxysmal kinesigenic dyskinesia (PKD) with benign infantile convulsion (BIC) and centrotemporal spikes (CTS) is very rare. A 10-year-old girl presented with a 3-year history of frequent attacks of staggering while laughing and of suddenly collapsing while walking. Interictal electroencephalogram (EEG) revealed bilateral CTS, but no changes in EEG were observed during movement. The patient's medical history showed afebrile seizures 6 months after birth, while the family history showed that the patient's mother and relatives on the mother's side had similar dyskinesia. Genetic testing demonstrated that the patient had a heterozygous mutation, c.649_650insC, in the PRRT2 gene. To our knowledge, this constitutes only the second report of a patient with PKD, BIC, CTS, and a PRRT2 mutation.

Induction of Inflammation Inhibits Taurine Transporter Activity in Murine Macrophage Cell Line

  • Kim, Jung-Hyun;Kim, Soyoung;Kim, Ha-Won;Kim, Byong-Kak
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 1998.11a
    • /
    • pp.156-157
    • /
    • 1998
  • Taurine is synthesized in the body or uptaken from dietary and is distributed in the various organs. It differs from other amino acids by virtue of the fact that a sulfonic acid group replaces the carboxyl group of what would be ${\beta}$-alanine. In order to function within the cell it must be transported into the cells by taurine transporter that is spanned 12 transmembrane domains. The human taurine transporter has long cytoplasmic carboxy and amino termini that may function as regulatory attachment sites for other proteins. Six potential protein kinase C(PKC) phosphorylation sites have been reported in human taurine transporter.

  • PDF

Comparison of Exon-boundary Old and Young Domains during Metazoan Evolution

  • Lee, Byung-Wook
    • Genomics & Informatics
    • /
    • v.7 no.2
    • /
    • pp.131-135
    • /
    • 2009
  • Domains are the building blocks of proteins. Exon shuffling is an important mechanism accounting for combination of a limited repertoire of protein domains in the evolution of multicellular species. A relative excess of domains encoded by symmetric exons in metazoan phyla has been presented as evidence of exon shuffling, and symmetric domains can be divided into old and new domains by determining the ages of the domains. In this report, we compare the spread, versatility, and subcellular localization of old and new domains by analyzing eight metazoan genomes and their respective annotated proteomes. We found that new domains have been expanding as multicellular organisms evolved, and this expansion was principally because of increases in class 1-1 domains amongst several classes of domain families. We also found that younger domains have been expanding in membranes and secreted proteins along with multi-cellular organism evolution. In contrast, old domains are located mainly in nuclear and cytoplasmic proteins. We conclude that the increasing mobility and versatility of new domains, in contrast to old domains, plays a significant role in metazoan evolution, facilitating the creation of secreted and transmembrane multidomain proteins unique to metazoa.

Functional Analysis of the First Mannosyltransferase (PIG-M) involved in Glycosylphosphatidylinositol Synthesis in Plasmodium falciparum

  • Kim, Youn Uck;Hong, Yeongjin
    • Molecules and Cells
    • /
    • v.24 no.2
    • /
    • pp.294-300
    • /
    • 2007
  • The mammalian glycosylphosphatidylinositol (GPI) anchor consists of three mannoses attached to acylated GlcN-(acyl)PI to form $Man_3$-GlcN-(acyl)PI. The first of the three mannose groups is attached to an intermediate to generate Man-GlcN-(acyl)PI by the first mannosyltransferase (GPI-MT-I). Mammalian and protozoan GPI-MT-I have different substrate specificities. PIG-M encodes the mammalial GPI-MT-I which has 423 amino acids and multiple transmembrane domains. In this work we cloned PIG-M homologues from humans, Plasmodium falciparum (PfPIG-M), and Saccharomyces cerevisiae (GPI14), to test whether they could complement GPI-MT-I-deficient mammalian cells, since this biosynthetic step is likely to be a good target for selective screening of inhibitors against many pathogenic organisms. PfPIG-M partially restored cell surface expression of the GPI-anchored protein CD59 in PIG-M deficient mammalian cells, and first mannose transfer activity in vitro; however, this was not the case for GPI14.

Homology Modeling of CCR 4: Novel Therapeutic Target and Preferential Maker for Th2 Cells

  • Shalini, M.;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
    • /
    • v.7 no.4
    • /
    • pp.234-240
    • /
    • 2014
  • C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.