Abstract：
:Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor that is essential for the normal development of the mammalian heart. Previous studies have shown that HOP, which consists entirely of a putative homeodomain, acts downstream of Nkx2.5 and associates with the serum response factor (SRF), repressing transcription from SRF-responsive genes. HOP is also able to recruit histone deacetylase (HDAC) activity, consistent with its ability to repress transcription. Unlike other classic homeodomain proteins, HOP does not appear to interact with DNA, although it has been unclear if this is because of an overall divergent structure or because of specific amino acid differences between HOP and other homeodomains. To work toward an understanding of HOP function, we have determined the 3D structure of full-length HOP and used a range of biochemical assays to define the parts of the protein that are functionally important for its repression activity. We show that HOP forms a classical homeodomain fold but that it cannot recognize double stranded DNA, a result that emphasizes the importance of caution in predicting protein function from sequence homology alone. We also demonstrate that two distinct regions on the surface of HOP are required for its ability to repress an SRF-driven reporter gene, and it is likely that these motifs direct interactions between HOP and partner proteins such as SRF- and HDAC-containing complexes. Our results demonstrate that the homeodomain fold has been co-opted during evolution for functions other than sequence-specific DNA binding and suggest that HOP functions as an adaptor protein to mediate transcriptional repression.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Kook H,Yung WW,Simpson RJ,Kee HJ,Shin S,Lowry JA,Loughlin FE,Yin Z,Epstein JA,Mackay JPdoi
10.1021/bi060641ssubject
Has Abstractpub_date
2006-09-05 00:00:00pages
10584-90issue
35eissn
0006-2960issn
1520-4995journal_volume
45pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:The solution conformation is presented for representatives of each of the major classes of asparaginyl oligosaccharides. In this report the conformation of alpha(1-3)-, alpha(1-2)-, beta(1-2)-, and beta(1-4)-linked units is described. The conformational properties of these glycopeptides were determined by high-resolut...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00284a021
更新日期：1983-07-19 00:00:00
abstract：:Biochemical and immunochemical data from the present investigation reveal the existence of a p85/p110 phosphoinositide 3-kinase (PI 3-kinase) in rat liver nuclei. 32P-Labeling of membrane phosphoinositides by incubating intact nuclei with [gamma-32P]ATP results in the formation of [32P]phosphatidyl-inositol 3,4, 5-tri...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi972551g
更新日期：1998-04-21 00:00:00
abstract：:Two highly conserved amino acid residues, an arginine and a glutamine, located near the C-terminal end of the gamma subunit, form a "catch" by hydrogen bonding with residues in an anionic loop on one of the three catalytic beta subunits of the bovine mitochondrial F1-ATPase [Abrahams, J. P., Leslie, A. G., Lutter, R.,...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi701581y
更新日期：2008-01-15 00:00:00
abstract：:We mutated residue 166, located in the putative Na(+) transport pathway between transmembrane segments 4 and 5 of human Na(+)/glucose cotransporter (hSGLT1), from alanine to cysteine (A166C). A166C was expressed in Xenopus laevis oocytes, and electrophysiological methods were used to assay function. The affinity for N...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi011026l
更新日期：2001-10-02 00:00:00
abstract：:The biochemical characteristics of the formation and disappearance of intercalator-induced DNA double-strand breaks (DSB) were studied in nuclei from mouse leukemia L1210 cells by using filter elution methodology [Bradley, M. O., & Kohn, K.W. (1979) Nucleic Acids Res. 7, 793-804]. The three intercalators used were 4'-...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00309a013
更新日期：1984-07-03 00:00:00
abstract：:Hydrophobic interaction of 8-anilino-1-naphthalene sulfonic acid (ANS) with proteins is one of the widely used methods for characterizing/detecting partially folded states of proteins. We have carried out a systematic investigation on the effect of ANS, a charged hydrophobic fluorescent dye, on structural properties o...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9907835
更新日期：1999-10-12 00:00:00
abstract：:The classical complement pathway, which plays a vital role in preventing infection, is initiated by the action of the serine proteases C1r and C1s. We have examined the hydrolysis of substrates representing cleavage sequences in the physiological substrates for C1s, C2 and C4. These studies showed that the P(1)'-P(4)'...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035507b
更新日期：2003-12-23 00:00:00
abstract：:Several recent studies have provided evidence that LIN28, a cytoplasmic RNA-binding protein, inhibits the biogenesis of members of the let-7 microRNA family at the Dicer step in both mammals and Caenorhabditis elegans. However, the precise mechanism of inhibition is still poorly understood. Here we report on an in vit...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi200851d
更新日期：2011-09-06 00:00:00
abstract：:The slowly hydrolyzed ATP analog adenosine 5'-(gamma-thiotriphosphate) (ATP gamma S) has been used in many studies of the muscle motor protein myosin in order to form a stable "weak binding" state analogous to the actin-S1-ATP complex However, the results from studies using ATP gamma S do not always agree with the res...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00049a018
更新日期：1995-12-12 00:00:00
abstract：:Guanidinium chloride- (GdmCl-) induced unfolding of beta-lactamase has been investigated by a combination of size-exclusion chromatography (SEC-FPLC) and usual optical methods. It has been shown that at low temperatures this protein unfolds through two equilibrium intermediates. The first of these intermediates is the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00176a006
更新日期：1994-03-15 00:00:00
abstract：:Hydrogenases are metalloenzymes that catalyze the reversible reduction of protons at unusual metal centers. This Current Topic discusses recent advances in elucidating the steps involved in the biosynthesis of the complex metal cluster at the [FeFe]-hydrogenase (HydA) active site, known as the H-cluster. The H-cluster...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi500210x
更新日期：2014-07-01 00:00:00
abstract：:Recently, we revealed the architecture of the clamp-loader-helicase (tau-DnaB) complex in Bacillus by atomic force microscopy imaging and constructed a structural model, whereby a pentameric clamp-loader interacts with the hexameric helicase. Crucial to this model is the assumption that the clamp-loader forms a pentam...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034955g
更新日期：2003-09-23 00:00:00
abstract：:A high molecular weight acyl coenzyme A (acyl-CoA) thioesterase, designated thioesterase II, has been purified 5300-fold from photoheterotrophically grown cells of Rhodopseudomonas sphaeroides. In contrast to R. sphaeroides acyl-CoA thioesterase I [Boyce, S.G., & Lueking, D.R. (1984) Biochemistry 23, 141-147], thioest...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00357a029
更新日期：1986-05-06 00:00:00
abstract：:Living cells contain a range of densely phosphorylated surfaces, including phospholipid membranes, ribonucleoproteins, and nucleic acid polymers. Hyperphosphorylated surfaces also accumulate in neurodegenerative diseases as neurofibrillar tangles. We have synthesized and structurally characterized a precisely patterne...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi500599a
更新日期：2014-07-08 00:00:00
abstract：:Protein binding specificities can be manipulated by redesigning contacts that already exist at an interface or by expanding the interface to allow interactions with residues adjacent to the original binding site. Previously, we developed a strategy, called AnchorDesign, for expanding interfaces around linear binding e...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.8b00408
更新日期：2018-07-31 00:00:00
abstract：:A 15-residue fragment within the major continuous domain of gp120 from HIV-1 that can bind independently to the CD4 receptor has been shown to have the property of behaving as a solvent polarity-dependent conformational switch. The switch behavior (cooperative transition from beta-sheet to helical conformation as a fu...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi952045w
更新日期：1996-01-16 00:00:00
abstract：:A variant of the Tetrahymena ribozyme that efficiently cleaves single-stranded DNA under simulated physiological conditions [Tsang, J., & Joyce, G. F. (1994) Biochemistry 33, 5966-5973] was evaluated as a potential therapeutic agent on the basis of its ability to cleave synthetic oligonucleotide substrates correspondi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi960845g
更新日期：1996-09-10 00:00:00
abstract：:Phosphatidylinositol-specific phospholipase C (PLC) enzymes catalyze the hydrolysis of phosphatidylinositol 4,5 bisphosphate in a two step reaction that involves a cyclic intermediate. The PLCbetafamily are activated by both the alpha and betagamma subunits of heterotrimeric G proteins. To determine which catalytic st...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0482607
更新日期：2005-02-22 00:00:00
abstract：:The mass-driven assembly of spectrin dimers to form tetramers involves two equal head-to-head alpha-beta associations and requires at least 30 degrees C for interconversion to occur readily. In this paper, the properties of tetramer formation were investigated using two complementary univalent peptides (the alpha I do...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00159a030
更新日期：1992-11-10 00:00:00
abstract：:As discovered by Grazi & Trombetta [Grazi, E., & Trombetta, G. (1978) Biochem. J. 175, 361], fructose-1,6-bisphosphate aldolase of rabbit muscle causes the slow formation of inorganic phosphate (Pi) and methylglyoxal when incubated with dihydroxyacetone phosphate (DHAP). In addition, these authors found an acid-labile...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00508a026
更新日期：1981-03-03 00:00:00
abstract：:By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00478a020
更新日期：1990-07-03 00:00:00
abstract：:Much interest has centered on two surface loops in the motor domain to explain the differences in enzymatic and mechanical properties of myosin isoforms. We showed that two invariant lysines at the C-terminal end of loop 2, which is part of the actin-binding interface, are required to obtain actin activation [Joel et ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034415j
更新日期：2003-08-05 00:00:00
abstract：:Indolicidin is an antimicrobial cationic peptide with broad-spectrum activity isolated from bovine neutrophils. An indolicidin analogue CP-11, ILKKWPWWPWRRK-NH(2), with improved activity against Gram-negative bacteria had increased positive charge and amphipathicity while maintaining the short length of the parent mol...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035643g
更新日期：2003-12-09 00:00:00
abstract：:By superimposing data obtained by photo-cross-linking RGD-containing ligands to the human alpha(V)beta(3) integrin onto the crystal structure of the ectopic domain of this receptor (Xiong et al. (2001) Science 294, 339-345), we have identified the binding site for the RGD triad within this integrin. We synthesized thr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi025690t
更新日期：2002-07-02 00:00:00
abstract：:Zn2+ is tetrahedrally bonded to the 4 nonadjacent thiols of each regulatory chain (Mr 17,000) near r-c contacts between catalytic (c) and regulatory chains (r) in aspartate transcarbamoylase (ATCase; c6r6). This paper reports on Zn2+ interactions with r dimer in the absence of stabilizing r-c contacts. After r2 and c3...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00480a019
更新日期：1990-07-17 00:00:00
abstract：:NG-Methyl-L-arginine (L-NMA) is one of the most commonly used inhibitors of the nitric oxide synthases (NOS). Results reported here demonstrate that L-NMA is an alternate substrate and a mechanism-based inhibitor of the inducible NOS purified from murine macrophages. The irreversible inhibition displays pseudo-first-o...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00088a020
更新日期：1993-09-21 00:00:00
abstract：:We have used a site-specific approach to investigate the mutagenic potential of (+)- and (-)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA adducts. Oligodeoxyribonucleotides (5'TCCTCCTG1G2-CCTCTC), modified at the exocyclic amino groups of G1 or G2, were incorporated into a single-stranded shuttle vector and intro...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9608875
更新日期：1996-12-24 00:00:00
abstract：:Aromatic amino acid aminotransferase (ArAT) from Escherichia coli was overexpressed in E. coli cells, purified, and characterized. The enzyme was similar to aspartate aminotransferase (AspAT) of E. coli in many aspects, such as gross protein structure and spectroscopic properties. The reactions of pyridoxal 5'-phospha...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00096a036
更新日期：1993-11-16 00:00:00
abstract：:Nitrogenase reduces N2 to NH3, but the mechanistic details are unclear. Diazene (N2H2), a proposed 2e-/2H+ intermediate on the reduction pathway, is labile under typical enzyme assay conditions, and no firm evidence is available on whether or not it can be reduced by or inhibit nitrogenase. In this paper, we compare t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi950964g
更新日期：1996-04-09 00:00:00
abstract：:Multidrug resistance protein (MRP) and P-glycoprotein (Pgp) are both members of the superfamily of ATP binding cassette plasma membrane drug transport proteins, which may be partly responsible for multidrug resistance of tumor cells. Although MRP has been identified as an organic anion transporter and Pgp as a transpo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9718043
更新日期：1998-02-24 00:00:00
