Abstract:
:The first transmembrane (TM1) helix in the red cell anion exchanger (AE1, Band 3, or SLC4A1) acts as an internal signal anchor that binds the signal recognition particle and directs the nascent polypeptide chain to the endoplasmic reticulum (ER) membrane where it moves from the translocon laterally into the lipid bilayer. The sequence N-terminal to TM1 forms an amphipathic helix that lies at the membrane interface and is connected to TM1 by a bend at Pro403. Southeast Asian ovalocytosis (SAO) is a red cell abnormality caused by a nine-amino acid deletion (Ala400-Ala408) at the N-terminus of TM1. Here we demonstrate, by extensive (∼4.5 μs) molecular dynamics simulations of TM1 in a model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membrane, that the isolated TM1 peptide is highly dynamic and samples the structure of TM1 seen in the crystal structure of the membrane domain of AE1. The SAO deletion not only removes the proline-induced bend but also causes a "pulling in" of the part of the amphipathic helix into the hydrophobic phase of the bilayer, as well as the C-terminal of the peptide. The dynamics of the SAO peptide very infrequently resembles the structure of TM1 in AE1, demonstrating the disruptive effect the SAO deletion has on AE1 folding. These results provide a precise molecular view of the disposition and dynamics of wild-type and SAO TM1 in a lipid bilayer, an important early biosynthetic intermediate in the insertion of AE1 into the ER membrane, and extend earlier results of cell-free translation experiments.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Fowler PW,Sansom MS,Reithmeier RAdoi
10.1021/acs.biochem.6b00966subject
Has Abstractpub_date
2017-02-07 00:00:00pages
712-722issue
5eissn
0006-2960issn
1520-4995journal_volume
56pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Signal transducer and activator of transcription factors (STATs) are proteins that can translocate into the nucleus, bind DNA, and activate gene transcription. STAT proteins play a crucial role in cell proliferation, apoptosis, and differentiation. The prevalent view is that STAT proteins are able to form dimers and b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501529x
更新日期:2015-09-08 00:00:00
abstract::Cyclic GMP phosphodiesterase, a key enzyme in phototransduction, is composed of P alpha beta and two P gamma subunits. Interaction of P gamma with P alpha beta or with the alpha subunit (T alpha) of transducin is crucial for the regulation of cGMP phosphodiesterase in retinal photoreceptors. Here we have investigated ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi973087i
更新日期:1998-04-28 00:00:00
abstract::Nuclear DNA of the marine chromophytic alga Olisthodiscus luteus was analyzed in this study. Reassociation kinetics analysis has shown that 440-nucleotide DNA fragments from the genome of this alga contain 4% foldback, 58% repetitive, and 34% single-copy sequences. Precise analysis using isolated single-copy DNA revea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00527a023
更新日期:1981-11-24 00:00:00
abstract::Maduropeptin (MDP) is a recently isolated antitumor antibiotic, consisting of an enediyne-containing chromophore embedded in a highly acidic protein. This holoantibiotic damages duplex DNA in vitro, producing a mixture of single- and double-strand breaks at selected sites. The chromophore, isolated as the methanol add...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00036a035
更新日期:1995-09-12 00:00:00
abstract::Factor VIII (FVIII) is the nonproteolytic cofactor for FIXa in the tenase complex of blood coagulation. FVIII is proteolytically activated by thrombin and FXa in vitro to form a heterotrimer with full procoagulant activity. Activated protein C inactivates thrombin-activated FVIII through cleavage adjacent to position ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00125a022
更新日期:1992-03-17 00:00:00
abstract::Thermodynamic equilibrium transition models in DSC are only applicable to reversible processes, but reversibility of the thermal transitions of proteins is comparatively rare because of intermolecular aggregation of denatured proteins and the degradation that occurs at high temperatures. The cupredoxin azurin from Pse...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0157621
更新日期:2002-01-22 00:00:00
abstract::The natural product hypericin is a photosensitive polycyclic aromatic dione compound, which has been widely investigated because of its virucidal and antitumor properties. Although it has been suggested that singlet oxygen or a radical species might be responsible for its biological action, its mechanism of action rem...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991147+
更新日期:1999-08-31 00:00:00
abstract::In the DNA recognition mode of C(2)H(2)-type zinc fingers, the finger-finger connection region, consisting of the histidine spacing (HX(3-5)H) and linker, would be important for determining the orientation of the zinc finger domains. To clarify the influence of spacing between two ligand histidines in the DNA binding,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035999s
更新日期:2004-05-25 00:00:00
abstract::The stability of three forms of glucoamylase from Aspergillus niger has been investigated by differential scanning and isothermal titration calorimetry: Glucoamylase 1 (GA1), which consists of a catalytic domain and a starch-binding domain (SBD) connected by a heavily O-glycosylated linker region; glucoamylase 2 (GA2)...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi990185q
更新日期:1999-05-11 00:00:00
abstract::The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide modifi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00002a001
更新日期:1995-01-17 00:00:00
abstract::Regulation of cellular processes by dietary nutrients is known to affect the likelihood of cancer development. One class of cancer-preventive nutrients, isothiocyanates (ITCs), derived from the consumption of cruciferous vegetables, is known to have various effects on cellular biochemistry. One target of ITCs is macro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi3005494
更新日期:2012-09-25 00:00:00
abstract::We report a new observation of the role of Escherichia coli single-strand DNA binding protein (SSB) in synthesis of primer RNA (pRNA) catalyzed by.E.coli primase on the SSB-coated phage G4oric template. Using a set of ATP priming substrates with reactive groups attached to the 5' gamma-phosphate on different length "a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972455f
更新日期:1998-03-17 00:00:00
abstract::Dog serum and colostral immunoglobulin A (IgA) and free secretory component from colostrum were isolated using affinity chromatography. Both serum and colostral IgA showed similar susceptibility to reduction with dithiothreitol, but only colostral IgA released the additional subunit, bound secretory component. This re...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00684a010
更新日期:1975-07-01 00:00:00
abstract::Cardiac troponin T (cTnT) is a myofibrillar protein essential for calcium-dependent contraction. This property has led to functional studies of developmentally expressed cTnT isoforms and mutants identified in patients with hypertrophic cardiomyopathy. The release of cTnT into the serum following myocardial infarction...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7012596
更新日期:2008-02-19 00:00:00
abstract::Two sites of ligand interaction in acetylcholinesterase (AChE) were first demonstrated in ligand binding studies and later confirmed by crystallography, site-specific mutagenesis, and molecular modeling: an acylation site at the base of the active site gorge and a peripheral site at its mouth. We recently introduced a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9813577
更新日期:1999-01-05 00:00:00
abstract::The fluorescence of the base analogue 2-aminopurine (2AP) was used to probe bacteriophage T4 DNA polymerase-induced conformational changes in the template strand produced during the nucleotide incorporation and proofreading reactions. 2AP fluorescence in DNA is quenched by 2AP interactions with neighboring bases, but ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051462y
更新日期:2005-12-06 00:00:00
abstract::A novel and efficient enzyme kinetics assay using electrospray ionization mass spectrometry was developed and applied to the bacterial carbohydrate sulfotransferase (NodST). NodST catalyzes the sulfuryl group transfer from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to chitobiose, generating 3'-phosphoadenosine 5'-ph...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020457g
更新日期:2002-11-05 00:00:00
abstract::Type II topoisomerases are responsible for DNA unlinking during DNA replication and chromosome segregation. Although eukaryotic enzymes are homodimers and prokaryotic enzymes are heterotetramers, both prokaryotic and eukaryotic type II topoisomerases belong to a single protein family. The amino- and carboxyl-terminal ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0155201
更新日期:2001-07-24 00:00:00
abstract::The objective of this work is to determine the molecular mechanism and regulation of short-chain acyl-CoA dehydrogenase (SCAD) from Megasphaera elsdenii. To achieve this, the gene coding for SCAD from M. elsdenii was cloned and sequenced. Site-directed mutagenesis was then used to identify an amino acid residue that i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00091a026
更新日期:1993-10-12 00:00:00
abstract::Ca2+-free crystals of sarcoplasmic reticulum Ca2+-ATPase have, up until now, been obtained in the presence of inhibitors such as thapsigargin (TG), bound to the transmembrane region of this protein. Here, we examined the consequences of such binding for the protein. We found that, after TG binding, an active site liga...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701855r
更新日期:2007-12-25 00:00:00
abstract::The spin label Tempo-maleimide, when "immobilized" in hemoglobin, is shown to exhibit motional fluctuation whose amplitude and/or frequency depend on temperature and solution conditions. These motional fluctuations are observable by several electron spin resonance techniques. For desalted hemoglobin the fluctuations a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00600a014
更新日期:1978-04-04 00:00:00
abstract::Structures of glycopeptides obtained by exhaustive Pronase digestion of high molecular weight (1.7 X 10(5)) salmon egg polysialoglycoprotein have been elucidated. Six principal glycopeptides isolated by gel chromatography and DEAE-Sephadex A-25 chromatography in the absence or presence of borate ion were analyzed for ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00341a029
更新日期:1985-09-24 00:00:00
abstract::Factor IX activation by factor XIa is thought to proceed through the singly-cleaved free intermediate, factor IX alpha. However, we observed no intermediate development during factor IX activation by factor XIa when using a low substrate to enzyme ratio (44:1 mol/mol). This result can be explained by one of two mechan...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962274y
更新日期:1997-04-08 00:00:00
abstract::Several experimental approaches have been employed to independently determine rates of dissociation for Escherichia coli RNA polymerase from the T7 bacteriophage A1, A2, A3, and D promoters. Heparin challenge measurements employing abortive initiation turnover rates as an index of promoter occupancy were carried out o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00552a023
更新日期:1980-05-27 00:00:00
abstract::Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion permeable channels. Our results demons...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00988
更新日期:2015-12-22 00:00:00
abstract::Sensory rhodopsin I (SRI) is a seven-transmembrane helix retinylidene protein that mediates color-sensitive phototaxis responses through its bound transducer HtrI in the archaeon Halobacterium salinarum. Deprotonation of the Schiff base attachment site of the chromophore accompanies formation of the SRI signaling stat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991180w
更新日期:1999-10-05 00:00:00
abstract::Effects of eight differently substituted 1,4-benzoquinones (BQs) on the quantum yield of photoactivation of oxygen evolution (reconstitution of the Mn cluster) were examined with wheat photosystem II (PSII) membranes depleted of the Mn cluster by treatment with 1.0 mM NH2OH. Illumination with 10 flashes at 0.25-s inte...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00117a032
更新日期:1992-01-21 00:00:00
abstract::125I-Labeled enterotoxin from Clostridium perfringens was utilized to characterize the association of the enterotoxin with cells isolated from rabbit intestine and tissue homogenates from liver, kidney, and brain. The enterotoxin was found to bind in a specific and saturable manner to cells from intestine and to tissu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00562a014
更新日期:1980-10-14 00:00:00
abstract::The binding of a ligand to cell surface receptors initiates a cascade of intracellular signals that generate responses to the external stimuli. Thus, this event plays a pivotal role in the mechanism of transmembrane signaling. Activin is a member of a cytokine family that is involved in diverse biological processes. T...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981939o
更新日期:1998-11-24 00:00:00
abstract::The structure of the vanadate-trapped ADP complex of a truncated head of Dictyostelium myosin II consisting of residues Asp 2-Asn 762 has been determined by molecular replacement at 1.9 A resolution and refined to a crystallographic R-factor of 19.4%. The crystals belong to the orthorhombic space group C2221 where a =...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952633+
更新日期:1996-04-30 00:00:00