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1.
Krempler A Kartarius S Günther J Montenarh M 《Cellular and molecular life sciences : CMLS》2005,62(12):1379-1387
2.
Wei Wang Jinyang Cai Yingliang Wu Li Hu Zongyun Chen Jun Hu Ze Chen Wenxin Li Mingxiong Guo Zan Huang 《Cellular and molecular life sciences : CMLS》2013,70(20):3947-3958
Previously, we found that two isoforms of the ZNF268 gene (ZNF268a and ZNF268b2, with and without the KRAB domain, respectively) might play distinct roles in normal epithelia and in cervical cancer. Here we further investigated that KRAB domain defined the function disparity in part by reinforcing nuclear localization of ZNF268a. We found that the A-box of KRAB alone retained major specific nuclear localization activity. In contrast, the B-box alone did not have nuclear localization activity but enhanced it significantly. Consistent with the critical function of the A-box, each mutation of six conserved residues (V9, V11, F13, E16, E17 and W18) in the A-box dramatically impaired nuclear localization activity. Furthermore, the unique nuclear localization activity of KRAB was verified in seven additional KRAB-containing zinc finger proteins (KRAB-ZFPs), suggesting that it is a universal feature of KRAB-ZFPs. Finally, KRAB exerted its unique nuclear localization activity by interacting with the RBCC domain of its corepressor KAP1. Our results have revealed a novel mechanism by which the KRAB domain reinforces nuclear localization of KRAB-ZFPs by interacting with KAP1. Our study also suggests that loss of the KRAB domain in KRAB-ZFPs due to aberrant alternative splicing might contribute to carcinogenesis. 相似文献
3.
Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state 总被引:1,自引:0,他引:1
Bergman T Zhang K Palmberg C Jörnvall H Auld DS 《Cellular and molecular life sciences : CMLS》2008,65(24):4019-4027
Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined
by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine
structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc
is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased
zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance
of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide
data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic
state, implying a functional nature for this zinc site.
Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008 相似文献
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5.
A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels 总被引:1,自引:1,他引:0
Tamzin M. Tanner Sarah Denayer Bart Geverts Nora Van Tilborgh Stefanie Kerkhofs Christine Helsen Lien Spans Vanessa Dubois Adriaan B. Houtsmuller Frank Claessens Annemie Haelens 《Cellular and molecular life sciences : CMLS》2010,67(11):1919-1927
6.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
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8.
F. E. Weber J. H. Dyer F. López García M. Werder T. Szyperski K. Wüthrich H. Hauser 《Cellular and molecular life sciences : CMLS》1998,54(7):751-759
The preform of the rabbit sterol carrier protein 2 (pre-rSCP2) was cloned, the uniformly 15N-labelled protein expressed in Escherichia coli and studied by three-dimensional 15N-resolved nuclear magnetic resonance spectroscopy. In spite of its low solubility in aqueous solution of only ∼0.3 mM, sequential
15N and 1H backbone resonance assignments were obtained for 105 out of the 143 residues. From comparison of the sequential and medium-range
nuclear Overhauser effects (NOEs) in the two proteins, all regular secondary structures previously determined in mature human
SCP2 (hSCP2) [Szyperski et al. (1993) FEBS Lett. 335: 18–26] were also identified in pre-rSCP2. Near-identity of the backbone 15N and 1H chemical shifts and 1 : 1 correspondence of 24 long-range NOEs to backbone amide groups in the two proteins show that the
residues 21 – 143 adopt the same globular fold in pre-rSCP2 and mature hSCP2. The N-terminal 20-residue leader peptide of pre-rSCP2 is flexibly disordered in solution and does not observably affect the conformation of the polypeptide segment 21 – 143.
Received 11 May 1998; accepted 15 May 1998 相似文献
9.
Ahlsén M Carlsson-Skwirut C Jonsson AP Cederlund E Bergman T Bang P 《Cellular and molecular life sciences : CMLS》2007,64(14):1870-1880
Proteolytic cleavage of insulin-like growth factor (IGF) binding protein (IGFBP)-3 during pregnancy is likely to have both
IGF-dependent and -independent effects on maternal, placental and fetal growth and metabolism. A 30-kDa proteolytic IGFBP-3
fragment was isolated from third trimester pregnancy human serum and identified by N- and C-terminal amino acid sequence analysis
and mass spectrometry to correspond to residues 1–212 of the parent protein. This fragment is the dominating IGFBP-3 immunoreactive
species in pregnancy serum. The 30-kDa fragment was also detected in serum of non-pregnant women where it coexists with intact
IGFBP-3. Using biosensor technology, (1–212)IGFBP-3 was found to have 11-fold lower affinity for IGF-I compared to intact
IGFBP-3, while a 4-fold decrease in affinity was found for IGF-II. Tests with des(1–3)IGF-I suggest fast binding of IGF-I
to the N-terminal region of IGFBP-3 and similar affinity to a slow binding site in the C-terminal region.
Received 24 April 2007; received after revision 11 June 2007; accepted 13 June 2007 相似文献
10.
Three classes of C2H2 zinc finger proteins 总被引:13,自引:0,他引:13
Iuchi S 《Cellular and molecular life sciences : CMLS》2001,58(4):625-635
C2H2 zinc finger proteins probably comprise the largest family of regulatory proteins in mammals. Most zinc fingers bind to a cognate DNA. In addition to DNA, many of the proteins also bind to RNA or protein, and some bind to RNA only. The binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. C2H2 zinc finger proteins contain from 1 to more than 30 figures. Based on the number and the pattern of the fingers, most of the proteins can be classified into one of three groups: triple-C2H2, multiple-adjacent-C2H2, and separated-paired-C2H2 finger proteins. In contrast to proteins with triple-C2H2 fingers, proteins with multiple-adjacent-C2H2 fingers can bind multiple, different ligands. Proteins with a number of separated-paired fingers bind to the target by means of only a single pair. 相似文献
11.
The zinc finger network of plants 总被引:6,自引:0,他引:6
12.
P. J. Lardone A. Carrillo-Vico P. Molinero A. Rubio J. M. Guerrero 《Cellular and molecular life sciences : CMLS》2009,66(3):516-525
Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism
of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE2 in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay
in PGE2-diminished IL-2 production. The decrease in IL-2 production after PGE2 and/or luzindole administration correlated with downregulation in the nuclear receptor RORα. We also highlighted a role of
cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE2 in the RORα expression. Finally, a significant RORα downregulation was observed in T cells permanently transfected with inducible
MT1 antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORα expression,
opening a new way to understand melatonin regulation in lymphocyte physiology.
Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008 相似文献
13.
Gineitis A Treigyte G Savickiene J Shanbhag VP Stigbrand T 《Cellular and molecular life sciences : CMLS》1999,55(2):317-326
The two-dimensional electrophoretic patterns of nuclear proteins and their tyrosine phosphorylation were compared for HL-60
cells before and after differentiation induction to granulocytes by dimethyl sulfoxide, all-trans retinoic acid and N
6,O
2-dibutyryl adenosine 3′5′-cyclic monophosphate. Regardless of the inducer used, some nuclear proteins, which are tyrosine-phosphorylated
in proliferating HL-60 cells, undergo gradual dephosphorylation 12–72 h after induction of differentiation, followed by drastic
dephosphorylation during maturation to granulocytes. At least 13 nuclear proteins with a molecular mass of 35–110 kDa are
dephosphorylated, and 6 nuclear proteins undergo tyrosine phosphorylation. Analysis of the nuclear proteins differentially
extracted by salt and detergents indicates that changes in their tyrosine phosphorylation during the maturation stage of differentiating
granulocytes occur mainly in proteins which are abundant in nucleoplasm, chromatin and residual nuclear structures. The abundance
of these proteins, residing in the nuclear structures, and their long-term modification in phosphorylation during the maturation
stages of differentiation strongly suggest that tyrosine phosphorylation of these proteins is involved in reorganization of
the differentiating cell nucleus.
Received 21 September 1998; received after revision 24 November 1998; accepted 3 December 1998 相似文献
14.
Heat shock protein 60: regulatory role on innate immune cells 总被引:1,自引:0,他引:1
Human heat shock protein 60 (Hsp60) exhibits immunoregulatory properties, primarily by inducing pro-inflammatory responses
in innate immune cells. Extensive analyses identified specific receptor structures for the interaction of Hsp60 with these
cells. The existence of distinct receptor structures responsible for Hsp60 binding and for Hsp60-induced release of pro-inflammatory
mediators has been demonstrated, implying that the interaction of Hsp60 with innate immune cells is a multifaceted process.
Distinct Hsp60 epitopes responsible for binding to innate immune cells and for the activation of these cells have been identified.
Depending on the cell-type, the amino acid (aa) region 481–500 or the regions aa241–260, aa391–410 and aa461–480 are involved
in Hsp60-binding to innate immune cells. An entirely different Hsp60-region, aa354–365 was found to bind lipopolysaccharide,
thereby mediating the pro-inflammatory effects of Hsp60. Because of its immunoregulatory properties, Hsp60 has been proposed
to act as intercellular danger signal, controlling innate and adaptive immune reactions.
Received 19 September 2006; received after revision 13 October 2006; accepted 13 December 2006 相似文献
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The survival of motor neuron ( SMN1) gene product, SMN, is detected both in the cytoplasm and in nuclear gems and cajal bodies. We show here that SMN exon 6 is essential both for formation of its nuclear foci and for its cytoplasmic localization. However, exon 7 inhibits the formation of SMN nuclear foci but promotes SMN cytoplasmic localization. More interestingly, we find that a random C-terminal tag of five or more amino acids downstream of exon 6 is sufficient to inhibit the occurrence of multiple nuclear foci and to promote cytoplasmic localization of SMNDelta7, the primary product of the SMN2 gene. Moreover, SMNDelta7 proteins that bear spinal muscular atrophy mutations in exon 6 either showed defects in nuclear foci formation or enhanced cytoplasmic localization. We conclude that exon 6 and exon 7 synergistically regulate SMN distribution that may require specific exon 6 motifs but is independent of specific sequences in exon 7. 相似文献
18.
Kraft B Johswich A Kauczor G Scharenberg M Gerardy-Schahn R Bakker H 《Cellular and molecular life sciences : CMLS》2011,68(24):4091-4100
The glycolipid specific Drosophila melanogaster β1,4-N-acetylgalactosaminyltransferase B (β4GalNAcTB) depends on a zinc finger DHHC protein family member named GalNAcTB pilot (GABPI)
for activity and translocation to the Golgi. The six-membrane spanning protein actually lacks the cysteine in the cytoplasmic
DHHC motif, displaying DHHS instead. Here we show that the whole conserved region around the DHHS sequence, which is essential
for palmitoylation in DHHC proteins, is not required for GABPI to interact with β4GalNAcTB. In contrast, the two luminal loops
between transmembrane domain 3–4 and 5–6 contain conserved amino acids, which are crucial for activity. Besides the dependence
on GABPI, β4GalNAcTB requires its exceptional short stem region for activity. A few hydrophobic amino acids positioned close
to the transmembrane domain are essential for the interaction with GABPI. Along with its catalytic domain, β4GalNAcTB, thus,
requires an area in its own stem region and two small luminal loops of GABPI as "add-on" domains. Moreover, some inactive
GABPI mutants could be rescued by fusion with β4GalNAcTB, indicating their importance in direct GABPI-β4GalNAcTB interaction. 相似文献
19.
Eleonora Dondossola Anna Gasparri Angela Bachi Renato Longhi Marie-Hélène Metz-Boutigue Bruno Tota Karen B. Helle Flavio Curnis Angelo Corti 《Cellular and molecular life sciences : CMLS》2010,67(12):2107-2118
Fibroblast adhesion can be modulated by proteins released by neuroendocrine cells and neurons, such as chromogranin A (CgA)
and its N-terminal fragment vasostatin-1 (VS-1, CgA1–78). We have investigated the mechanisms of the interaction of VS-1 with fibroblasts and of its pro-adhesive activity and have
found that the proadhesive activity of VS-1 relies on its interaction with the fibroblast membrane via a phospholipid-binding
amphipathic α-helix located within residues 47–66, as well as on the interaction of the adjacent C-terminal region 67–78,
which is structurally similar to ezrin–radixin–moesin-binding phosphoprotein 50 (a membrane-cytoskeleton adapter protein),
with other cellular components critical for the regulation of cell cytoskeleton. 相似文献
20.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献