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排序方式: 共有197条查询结果,搜索用时 15 毫秒
21.
Misha Golynskiy Sheng Li Virgil L. WoodsJr Seth M. Cohen 《Journal of biological inorganic chemistry》2007,12(5):699-709
The manganese transport regulator (MntR) of Bacillus subtilis is a metalloregulatory protein responsible for regulation of genes involved in manganese uptake by this organism. MntR belongs
to the iron-responsive DtxR family, but is allosterically regulated by manganese and cadmium ions. Having previously characterized
the metal binding affinities of this protein as well as the DNA-binding activation profiles for the relevant metal ions, we
have focused the current study on investigating the structural changes of MntR in solution upon binding divalent transition
metal ions. Deuterium exchange mass spectrometry was utilized to investigate the deuterium exchange dynamics between apo-MntR,
Co2+-MntR, Cd2+-MntR, and Mn2+-MntR. Comparing the rates of deuteration of each metal-bound form of MntR reveals that the N-terminal DNA-binding motif is
more mobile in solution than the C-terminal dimerization domain. Furthermore, significant protection from deuterium exchange
is observed in the helices that contribute metal-chelating amino acids to form the metal binding site of MntR. In contrast,
the bulk of the DNA-binding winged helix–turn–helix motif shows no difference in deuterium exchange upon metal binding. Mapping
of the deuteration patterns onto the crystal structures of MntR yields insight into how metal binding affects the protein
structure and complements earlier studies on the mechanism of MntR. Metal binding acts to rigidify MntR, thereby limiting
the mobility of the protein and reducing the entropic cost of DNA binding.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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Burns-Hamuro LL Hamuro Y Kim JS Sigala P Fayos R Stranz DD Jennings PA Taylor SS Woods VL 《Protein science : a publication of the Protein Society》2005,14(12):2982-2992
The structure of an AKAP docked to the dimerization/docking (D/D) domain of the type II (RIIalpha) isoform of protein kinase A (PKA) has been well characterized, but there currently is no detailed structural information of an AKAP docked to the type I (RIalpha) isoform. Dual-specific AKAP2 (D-AKAP2) binds in the nanomolar range to both isoforms and provided us with an opportunity to characterize the isoform-selective nature of AKAP binding using a common docked ligand. Hydrogen/deuterium (H/D) exchange combined with mass spectrometry (DXMS) was used to probe backbone structural changes of an alpha-helical A-kinase binding (AKB) motif from D-AKAP2 docked to both RIalpha and RIIalpha D/D domains. The region of protection upon complex formation and the magnitude of protection from H/D exchange were determined for both interacting partners in each complex. The backbone of the AKB ligand was more protected when bound to RIalpha compared to RIIalpha, suggesting an increased helical stabilization of the docked AKB ligand. This combined with a broader region of backbone protection induced by the AKAP on the docking surface of RIalpha indicated that there were more binding constraints for the AKB ligand when bound to RIalpha. This was in contrast to RIIalpha, which has a preformed, localized binding surface. These distinct modes of AKAP binding may contribute to the more discriminating nature of the RIalpha AKAP-docking surface. DXMS provides valuable structural information for understanding binding specificity in the absence of a high-resolution structure, and can readily be applied to other protein-ligand and protein-protein interactions. 相似文献
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Hsu YH Burke JE Stephens DL Deems RA Li S Asmus KM Woods VL Dennis EA 《The Journal of biological chemistry》2008,283(15):9820-9827
The GIVA phospholipase A(2) (PLA(2)) contains two domains: a calcium-binding domain (C2) and a catalytic domain. These domains are linked via a flexible tether. GIVA PLA(2) activity is Ca(2+)-dependent in that calcium binding promotes protein docking to the phospholipid membrane. In addition, the catalytic domain has a lid that covers the active site, presumably regulating GIVA PLA(2) activity. We now present studies that explore the dynamics and conformational changes of this enzyme in solution utilizing peptide amide hydrogen/deuterium (H/D) exchange coupled with liquid chromatography-mass spectrometry (DXMS) to probe the solvent accessibility and backbone flexibility of the C2 domain, the catalytic domain, and the intact GIVA PLA(2). We also analyzed the changes in H/D exchange of the intact GIVA PLA(2) upon Ca(2+) binding. The DXMS results showed a fast H/D-exchanging lid and a slow exchanging central core. The C2 domain showed two distinct regions: a fast exchanging region facing away from the catalytic domain and a slow exchanging region present in the "cleft" region between the C2 and catalytic domains. The slow exchanging region of the C2 domain is in tight proximity to the catalytic domain. The effects of Ca(2+) binding on GIVA PLA(2) are localized in the C2 domain and suggest that binding of two distinct Ca(2+) ions causes tightening up of the regions that surround the anion hole at the tip of the C2 domain. This conformational change may be the initial step in GIVA PLA(2) activation. 相似文献
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Yang J Wu J Steichen JM Kornev AP Deal MS Li S Sankaran B Woods VL Taylor SS 《Journal of molecular biology》2012,415(4):666-679
Eukaryotic protein kinases (EPKs) feature two coevolved structural segments, the Activation segment, which starts with the Asp-Phe-Gly (DFG) and ends with the Ala-Pro-Glu (APE) motifs, and the helical GHI subdomain that comprises αG-αH-αI helices. Eukaryotic-like kinases have a much shorter Activation segment and lack the GHI subdomain. They thus lack the conserved salt bridge interaction between the APE Glu and an Arg from the GHI subdomain, a hallmark signature of EPKs. Although the conservation of this salt bridge in EPKs is well known and its implication in diseases has been illustrated by polymorphism analysis, its function has not been carefully studied. In this work, we use murine cAMP-dependent protein kinase (protein kinase A) as the model enzyme (Glu208 and Arg280) to examine the role of these two residues. We showed that Ala replacement of either residue caused a 40- to 120-fold decrease in catalytic efficiency of the enzyme due to an increase in K(m)(ATP) and a decrease in k(cat). Crystal structures, as well as solution studies, also demonstrate that this ion pair contributes to the hydrophobic network and stability of the enzyme. We show that mutation of either Glu or Arg to Ala renders both mutant proteins less effective substrates for upstream kinase phosphoinositide-dependent kinase 1. We propose that the Glu208-Arg280 pair serves as a center hub of connectivity between these two structurally conserved elements in EPKs. Mutations of either residue disrupt communication not only between the two segments but also within the rest of the molecule, leading to altered catalytic activity and enzyme regulation. 相似文献
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White-nose syndrome and wing damage index scores among summer bats in the northeastern United States
White-nose syndrome (WNS) adversely affects millions of bats hibernating in caves of the eastern United States. Beginning in 2009, the US Fish and Wildlife Service supported use of a wing damage index (WDI) scoring system (scale of 0 to 3, or no damage to severe) to assess wing damage of bats captured during summer. Based on bat captures at 459 mist net sites in Pennsylvania, New York, Maryland, Virginia, and New Jersey, USA, we questioned whether WDI scores varied by species group, date, and distance to the closest known affected hibernaculum. We also compared relative health (body mass index [BMI] scores) to WDI scores. Of 3,419 bats (nine species), only four individuals (0.1%; little brown [Myotis lucifugus] and northern bats [Myotis septentrionalis]) were scored as a 3 and 47 (1.4%; big brown [Eptesicus fuscus], little brown, and northern bats) as a 2. All tree bats (eastern red [Lasiurus borealis], hoary [Lasiurus cinereus], and silver-haired bats [Lasionycteris noctivagans]) scored a 0 or 1, suggesting that these species were not affected by WNS. The average WDI score decreased as summer progressed, although trends were weak. Average WDI score and number of bats with class 2 and 3 damage increased with proximity to a known WNS-positive hibernaculum. Similarly, the number of bats with severe wing damage (scoring 2 or 3) was greater at sites closer to infected hibernacula, but little variance was explained by the trend. When species-specific BMI was examined, trends were consistent by sex (female BMI scores were higher than those of males), but no relationship was discovered between BMI and WDI scores. We conclude that, at this larger geographic scale, WDI is not a clear indicator of bat health. 相似文献