Abstract：
:Methylated DNA binding protein 2 (MeCP2) is a methyl CpG binding protein whose key role is the recognition of epigenetic information encoded in DNA methylation patterns. Mutation or misregulation of MeCP2 function leads to Rett syndrome as well as a variety of other autism spectrum disorders. Here, we have analyzed in detail the properties of six individually expressed human MeCP2 domains spanning the entire protein with emphasis on their interactions with each other, with DNA, and with nucleosomal arrays. Each domain contributes uniquely to the structure and function of the full-length protein. MeCP2 is approximately 60% unstructured, with nine interspersed alpha-molecular recognition features (alpha-MoRFs), which are polypeptide segments predicted to acquire secondary structure upon forming complexes with binding partners. Large increases in secondary structure content are induced in some of the isolated MeCP2 domains and in the full-length protein by binding to DNA. Interactions between some MeCP2 domains in cis and trans seen in our assays likely contribute to the structure and function of the intact protein. We also show that MeCP2 has two functional halves. The N-terminal portion contains the methylated DNA binding domain (MBD) and two highly disordered flanking domains that modulate MBD-mediated DNA binding. One of these flanking domains is also capable of autonomous DNA binding. In contrast, the C-terminal portion of the protein that harbors at least two independent DNA binding domains and a chromatin-specific binding domain is largely responsible for mediating nucleosomal array compaction and oligomerization. These findings led to new mechanistic and biochemical insights regarding the conformational modulations of this intrinsically disordered protein, and its context-dependent in vivo roles.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Ghosh RP,Nikitina T,Horowitz-Scherer RA,Gierasch LM,Uversky VN,Hite K,Hansen JC,Woodcock CLdoi
10.1021/bi9019753subject
Has Abstractpub_date
2010-05-25 00:00:00pages
4395-410issue
20eissn
0006-2960issn
1520-4995journal_volume
49pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:Calmodulin (CaM) is composed of two EF-hand domains tethered by a flexible linker. Upon Ca2+-binding, a fragment of CaM encompassing EF-hands 2 and 3 (CaM2/3; residues 46-113) folds into a structure remarkably similar to the N- and C-domains of CaM. In this study, we demonstrate that Ca2+-ligated CaM2/3 can also bind ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi700265j
更新日期：2007-07-24 00:00:00
abstract：:Kynureninase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the hydrolytic cleavage of l-kynurenine to give l-alanine and anthranilic acid. beta-Benzoyl-l-alanine, the analogue of l-kynurenine lacking the aromatic amino group, was shown to a good substrate for kynureninase from Pseudomonas fluorescens, an...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi100955b
更新日期：2010-09-14 00:00:00
abstract：:RSC (remodel the structure of chromatin) is an essential chromatin remodeler of Saccharomyces cerevisiae that has been shown to have DNA translocase properties. We studied the DNA binding properties of a "trimeric minimal RSC" (RSCt) of the RSC chromatin remodeling complex and the effect of nucleotides on this interac...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi200837b
更新日期：2011-09-20 00:00:00
abstract：:The flavoenzyme tryptophan 2-monooxygenase catalyzes the oxidation of tryptophan to indoleacetamide, carbon dioxide, and water. The enzyme is a homologue of l-amino acid oxidase. In the structure of l-amino acid oxidase complexed with aminobenzoate, Tyr372 hydrogen bonds with the carboxylate of the inhibitor in the ac...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035300i
更新日期：2003-12-02 00:00:00
abstract：:The hinge domain encompasses amino acids 51-60 of lactose repressor (LacI) and plays an important role in its regulatory interaction with operator DNA. This segment makes both hinge-DNA and hinge-hinge' contacts that are critical to DNA binding. Furthermore, this small region serves as a central element in communicati...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0114067
更新日期：2001-12-25 00:00:00
abstract：:The acid-induced arginine decarboxylase is part of an enzymatic system in Escherichia coli that contributes to making this organism acid resistant. The arginine decarboxylase is a vitamin B(6)-dependent enzyme that is active at acidic pH. It consumes a proton in the decarboxylation of arginine to agmatine, and by work...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi900075d
更新日期：2009-05-12 00:00:00
abstract：:HK31 (S565-K595) has previously been shown to encompass the binding domain for plasma prekallikrein (PK) within domain 6 of high molecular weight kininogen (HK). The complementary binding domain for HK within PK is mapped to PK56 (F56-G86), in the apple 1 domain, and to PK266 (K266-C295), in the apple 4 domain. Isothe...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi960547j
更新日期：1996-10-01 00:00:00
abstract：:For the study of the protein--protein and protein--nucleic acid interactions in the assembly of virus particles, laser Raman spectra have been obtained in H2O and D2O solutions and as a function of temperature for the following Salmonella phage P22 components: mature phage particles, isolated mature phage DNA, mature ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00259a023
更新日期：1982-08-03 00:00:00
abstract：:Tyramine β-monooxygenase (TβM), the insect homologue of dopamine β-monooxygenase, is a neuroregulatory enzyme that catalyzes the β-hydroxylation of tyramine to yield octopamine. Mutation of the methionine (Met) ligand to Cu(M) of TβM, Met471Cys, yielded a form of TβM that is catalytically active but susceptible to ina...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi300456f
更新日期：2012-09-25 00:00:00
abstract：:The iron-chelating peptide vibriobactin of the pathogenic Vibrio cholerae is assembled by a four-subunit nonribosomal peptide synthetase complex, VibE, VibB, VibH, and VibF, using 2,3-dihydroxybenzoate and L-threonine as precursors to two 2,3-dihydroxyphenyl- (DHP-) methyloxazolinyl groups in amide linkage on a norspe...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi010937s
更新日期：2001-09-04 00:00:00
abstract：:The mitochondrial folate transporter (MFT) was previously identified in human and hamster cells. Sequence homology of this protein with the inner mitochondrial membrane transporters suggested a domain structure in which the N- and C-termini of the protein are located on the mitochondrial intermembrane-facing surface, ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi062191+
更新日期：2007-02-13 00:00:00
abstract：:The pre-steady-state reaction of indole and L-serine with the alpha 2 beta 2 complex of Escherichia coli tryptophan synthase has been investigated under different premixing conditions with rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy for the spectral range 300-550 nm. When alpha 2 beta 2 was mixed with i...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00357a032
更新日期：1986-05-06 00:00:00
abstract：:We have characterized the importance of size, sulfation, and anticoagulant activity of heparin in release of basic fibroblast growth factor (bFGF) from the subendothelial extracellular matrix (ECM) and the luminal surface of the vascular endothelium. For this purpose, 125I-bFGF was first incubated with ECM and conflue...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00122a027
更新日期：1992-02-25 00:00:00
abstract：:Crk-II is a signaling adaptor protein that is involved in many cellular processes including apoptosis, proliferation, and differentiation. It has a modular domain architecture consisting of an Src homology 2 domain (SH2) followed by two Src homology 3 (SH3) domains. The structures and ligand-binding properties of the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi060590z
更新日期：2006-07-25 00:00:00
abstract：:We have obtained the 470 MHz 19F NMR spectra of wild type [4-F]Trp-labeled myoglobins (MbCO, MbO2, deoxyMb, metMb, and MbCN) and hemoglobins (HbCO, HbO2, and deoxyHb), as well as those of several mutants (W7F Mb, betaW15F Hb, betaW37S Hb, and betaY130F Hb, all as the carbonmonoxy adducts), prepared via site-directed m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi961664h
更新日期：1997-03-25 00:00:00
abstract：:Calcium dynamics and its linked molecular interactions cause a variety of biological responses; thus, exploiting techniques for detecting both concurrently is essential. Here we describe a method for measuring the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and protein-protein interactions within the same cell, using...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi200287x
更新日期：2011-05-31 00:00:00
abstract：:An inhibitor of the insulin receptor tyrosine kinase (IRTK), (hydroxy-2-naphthalenyl-methyl) phosphonic acid, was designed and synthesized and was shown to be an inhibitor of the biological effects of insulin in vitro. With a wheat germ purified human placental insulin receptor preparation, this compound inhibited the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00439a053
更新日期：1989-06-27 00:00:00
abstract：:Lipid-protein interactions in bovine rod outer segment disk membranes have been studied by using a series of eight stearic acid spin-label probes which were labeled at different carbon atom positions in the chain. In randomly oriented membrane dispersions, the electron spin resonance (ESR) spectra of the C-8, C-9, C-1...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00375a005
更新日期：1987-01-13 00:00:00
abstract：:Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is regulated via multiple elements located in intron 1, including element F which contains an E-box. In this study we have identified and characterized the factors that are capable of binding to element F. Yeast one-hybrid screening using eleme...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002847d
更新日期：2001-07-31 00:00:00
abstract：:To investigate the effect of a reduced level of selenocysteine (Sec) tRNA[Ser]Sec in selenoprotein biosynthesis, two mouse embryonic stem (ES) cell lines heterozygous for the corresponding gene were generated by homologous recombination of the host genome with targeting vectors encoding a deleted or a disrupted tRNA[S...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi970608t
更新日期：1997-07-15 00:00:00
abstract：:Under conditions where muscle actin only partially polymerizes, or where it does not polymerize at all, a significant enhancement of polymerization was observed if equimolar phalloidin was also present. The increased extent of polymerization in the the presence of phalloidin can be explained by the reduced critical ac...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00507a006
更新日期：1981-02-17 00:00:00
abstract：:Heparan sulfate (HS) proteoglycans (PGs) interact with a number of extracellular signaling proteins, thereby playing an essential role in the regulation of many physiological processes. These interactions are important for both normal signal transduction and regulation of the tissue distribution of signaling molecules...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi6025424
更新日期：2007-04-03 00:00:00
abstract：:The aryl hydrocarbon receptor (AhR) is an intracellular receptor protein that regulates gene transcription in response to both man-made and natural ligands. A modular transactivaton domain (TAD) has been mapped to the 304 C-terminal amino acids and consists of acidic, Q-rich, and P/S/T-rich subdomains. We have used st...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0487701
更新日期：2005-01-18 00:00:00
abstract：:Biological actions of insulin are initiated by activation of the insulin receptor tyrosine kinase. Protein tyrosine phosphatases (PTPases) PTP1B and PTPalpha are known to dephosphorylate the insulin receptor and may contribute to insulin resistance in diseases such as diabetes. We previously reported that overexpressi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9816103
更新日期：1999-01-05 00:00:00
abstract：:Troponin T (TnT) is an essential element in the thin filament-based regulatory system of striated muscle. Alternative mRNA splicing generates multiple TnT isoforms with primary structural differences in the NH2-terminal region. The functional significance of this hypervariable NH2-terminal domain and the developmental...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9812322
更新日期：1998-10-13 00:00:00
abstract：:Human hephaestin (Hp) is a transmembrane protein that has been implicated in duodenal iron export. Mutations in the murine hephaestin gene (sla) produce microcytic, hypochromic anemia that is refractory to oral iron therapy. Hp shares approximately 50% sequence identity with the plasma multicopper ferroxidase cerulopl...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi051559k
更新日期：2005-11-15 00:00:00
abstract：:The locations of RNA-RNA cross-links in 16S rRNA were determined after in vivo incorporation of 4-thiouridine (s(4)U) into RNA in a strain of Escherichia coli deficient in pyrimidine synthesis and irradiation at >320 nm. This was done as an effort to find RNA cross-links different from UVB-induced cross-links that wou...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi049702h
更新日期：2004-07-20 00:00:00
abstract：:The formation of pseudouridine (psi) on U5 small nuclear RNA (U5 snRNA) was studied using an in vitro modification system. Labeled U5 RNA, synthesized in vitro and therefore unmodified, was incubated in reactions containing S100 and/or nuclear extracts (NE) from HeLa cells, and the levels of psi were determined. There...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00200a025
更新日期：1994-08-30 00:00:00
abstract：:p-(Chloromercuri)benzoic acid inhibited the catalytic activity of Bacillus stearothermophilus farnesyl diphosphate synthase (FPP synthase), which contains only two cysteine residues at positions 73 and 289. In order to explore the role of the cysteine residues, either or both of them were replaced with phenylalanine o...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00208a015
更新日期：1994-10-25 00:00:00
abstract：:Calcineurin, a Ca2+, calmodulin-dependent protein phosphatase, was recently found to bind with high affinity to two different immunosuppressant binding proteins (immunophilins) with absolute dependence on the presence of the immunosuppressants FK506 or cyclosporin A (CsA) [Liu et al. (1991) Cell 66, 807-815]. The bind...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00131a002
更新日期：1992-04-28 00:00:00
