Interplay of Specific Trans- and Juxtamembrane Interfaces in Plexin A3 Dimerization and Signal Transduction.

Abstract:

:Plexins are transmembrane proteins that serve as guidance receptors during angiogenesis, lymphangiogenesis, neuronal development, and zebrafish fin regeneration, with a putative role in cancer metastasis. Receptor dimerization or clustering, induced by extracellular ligand binding but modulated in part by the plexin transmembrane (TM) and juxtamembrane (JM) domains, is thought to drive plexin activity. Previous studies indicate that isolated plexin TM domains interact through a conserved, small-x3-small packing motif, and the cytosolic JM region interacts through a hydrophobic heptad repeat; however, the roles and interplay of these regions in plexin signal transduction remain unclear. Using an integrated experimental and simulation approach, we find disruption of the small-x3-small motifs in the Danio rerio Plexin A3 TM domain enhances dimerization of the TM-JM domain by enhancing JM-mediated dimerization. Furthermore, mutations of the cytosolic JM heptad repeat that disrupt dimerization do so even in the presence of TM domain mutations. However, mutations to the small-x3-small TM interfaces also disrupt Plexin A3 signaling in a zebrafish axonal guidance assay, indicating the importance of this TM interface in signal transduction. Collectively, our experimental and simulation results demonstrate that multiple TM and JM interfaces exist in the Plexin A3 homodimer, and these interfaces independently regulate dimerization that is important in Plexin A3 signal transduction.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Barton R,Khakbaz P,Bera I,Klauda JB,Iovine MK,Berger BW

doi

10.1021/acs.biochem.6b00517

subject

Has Abstract

pub_date

2016-09-06 00:00:00

pages

4928-38

issue

35

eissn

0006-2960

issn

1520-4995

journal_volume

55

pub_type

杂志文章
  • Substrate connectivity effects in the transition state for cytidine deaminase.

    abstract::The binding properties of substrates and competitive inhibitors of Escherichia coli cytidine deaminase are compared with those of the fragments obtained by cutting these ligands at several positions including the glycosidic bond. In contrast with the normal substrate cytidine (kcat/Km = 2.6 x 10(6) M-1 s-1), cytosine ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi980959n

    authors: Carlow D,Wolfenden R

    更新日期:1998-08-25 00:00:00

  • Dynamics of light-induced conformational changes of the phoborhodopsin/transducer complex formed in the n-dodecyl beta-D-maltoside micelle.

    abstract::A complex of photoreceptor phoborhodopsin (ppR; also called sensory rhodopsin II) and its cognate halobacterial transducer II (pHtrII) existing in the plasma membrane mediates the light signal to the cytoplasm in the earliest step of negative phototaxis in Natronomonas pharaonis. We have investigated the dynamics of t...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi602482s

    authors: Taniguchi Y,Ikehara T,Kamo N,Yamasaki H,Toyoshima Y

    更新日期:2007-05-08 00:00:00

  • Membrane curvature, lipid segregation, and structural transitions for phospholipids under dual-solvent stress.

    abstract::Amphiphiles respond both to polar and to nonpolar solvents. In this paper X-ray diffraction and osmotic stress have been used to examine the phase behavior, the structural dimensions, and the work of deforming the monolayer-lined aqueous cavities formed by mixtures of dioleoylphosphatidylethanolamine (DOPE) and dioleo...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00453a010

    authors: Rand RP,Fuller NL,Gruner SM,Parsegian VA

    更新日期:1990-01-09 00:00:00

  • 3'- and 5'-strand cleavage reactions catalyzed by the Fpg protein from Escherichia coli occur via successive beta- and delta-elimination mechanisms, respectively.

    abstract::The Fpg protein from Escherichia coli is a multifunctional protein that excises damaged purine bases from DNA to generate aldehydic abasic sites and then catalyzes the successive cleavage of the phosphodiester bonds first on the 3'-side and then on the 5'-side of the abasic site to generate 5'- and 3'-phosphate ends, ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9522662

    authors: Bhagwat M,Gerlt JA

    更新日期:1996-01-16 00:00:00

  • Three-dimensional structure of potato carboxypeptidase inhibitor in solution. A study using nuclear magnetic resonance, distance geometry, and restrained molecular dynamics.

    abstract::The solution conformation of potato carboxypeptidase inhibitor (CPI) has been investigated by 1H NMR spectroscopy. The spectrum is assigned in a sequential manner by using two-dimensional NMR techniques to identify through-bond and through-space (less than 5 A) connectivities. A set of 309 approximate interproton dist...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00398a069

    authors: Clore GM,Gronenborn AM,Nilges M,Ryan CA

    更新日期:1987-12-01 00:00:00

  • 31P NMR studies of ATP synthesis and hydrolysis kinetics in the intact myocardium.

    abstract::The origin of the nuclear magnetic resonance (NMR)-measurable ATP in equilibrium Pi exchange and whether it can be used to determine net oxidative ATP synthesis rates in the intact myocardium were examined by detailed measurements of ATP in equilibrium Pi exchange rates in both directions as a function of the myocardi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00397a045

    authors: Kingsley-Hickman PB,Sako EY,Mohanakrishnan P,Robitaille PM,From AH,Foker JE,Uğurbil K

    更新日期:1987-11-17 00:00:00

  • Molecular dynamics simulations of the unfolding of barnase in water and 8 M aqueous urea.

    abstract::Molecular dynamics simulations of barnase have been conducted both in water and in 8 M urea solution for 500 ps at 25 degrees C and for 2000 ps at 85 degrees C. The final structure of the aqueous simulation at room temperature matches closely the structure obtained by NMR and the experimentally observed protections fr...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi970096i

    authors: Tirado-Rives J,Orozco M,Jorgensen WL

    更新日期:1997-06-17 00:00:00

  • Impact of Rett Syndrome Mutations on MeCP2 MBD Stability.

    abstract::Rett syndrome causing missense mutations in the methyl-CpG-binding domain (MBD) of methyl CpG-binding protein 2 (MeCP2) were investigated both in silico and in vitro to reveal their effect on protein stability. It is demonstrated that the vast majority of frequently occurring mutations in the human population indeed a...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.5b00790

    authors: Kucukkal TG,Yang Y,Uvarov O,Cao W,Alexov E

    更新日期:2015-10-20 00:00:00

  • The observed inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate for HIV-1 reverse transcriptase depends on the length of the poly(rA) region of the template.

    abstract::The inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) against HIV-1 reverse transcriptase (HIV-1 RT) has been further evaluated. The results indicate that the previously reported low Ki values for AZTTP against HIV-1 RT (2.35 nM) are due neither to the to the direct tight binding of AZTTP to HIV...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00120a013

    authors: Ma QF,Bathurst IC,Barr PJ,Kenyon GL

    更新日期:1992-02-11 00:00:00

  • Structural studies of yeast Δ(1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): active site flexibility and oligomeric state.

    abstract::The proline catabolic enzyme Δ(1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1) catalyzes the NAD(+)-dependent oxidation of γ-glutamate semialdehyde to l-glutamate. In Saccharomyces cerevisiae, ALDH4A1 is encoded by the PUT2 gene and known as Put2p. Here we report the steady-state kinetic parameters of the purified ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi500048b

    authors: Pemberton TA,Srivastava D,Sanyal N,Henzl MT,Becker DF,Tanner JJ

    更新日期:2014-03-04 00:00:00

  • Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1.

    abstract::Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi0200514

    authors: Bednarek MA,Hreniuk DL,Tan C,Palyha OC,MacNeil DJ,Van der Ploeg LH,Howard AD,Feighner SD

    更新日期:2002-05-21 00:00:00

  • Profiling Aglycon-Recognizing Sites of UDP-glucose:glycoprotein Glucosyltransferase by Means of Squarate-Mediated Labeling.

    abstract::Because of its ability to selectively glucosylate misfolded glycoproteins, UDP-glucose:glycoprotein glucosyltransferase (UGGT) functions as a folding sensor in the glycoprotein quality control system in the endoplasmic reticulum (ER). The unique property of UGGT derives from its ability to transfer a glucose residue t...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.5b00785

    authors: Ohara K,Takeda Y,Daikoku S,Hachisu M,Seko A,Ito Y

    更新日期:2015-08-11 00:00:00

  • Enzymatic activation of DNA cleavage by dynemicin A and synthetic analogs.

    abstract::Dynemicin A (1), a member of the enediyne family of natural products, binds to double-stranded DNA (K(B) approximately 10(4) M(-1)) and in the presence of millimolar concentrations of a reducing cofactor such as NADPH or GSH reacts to cleave DNA. In this work, we show that the two flavin-based enzymes ferredoxin-NADP+...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi962976n

    authors: Myers AG,Kort ME,Cohen SB,Tom NJ

    更新日期:1997-04-01 00:00:00

  • Stability effects of increasing the hydrophobicity of solvent-exposed side chains in staphylococcal nuclease.

    abstract::A total of fifty single site surface phenylalanine substitution mutants have been made in the model protein staphylococcal nuclease. The fifty residues that were replaced with phenylalanine were chosen to give a broad sampling of solvent accessibility, secondary structure, and backbone conformations. The change in the...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9725069

    authors: Schwehm JM,Kristyanne ES,Biggers CC,Stites WE

    更新日期:1998-05-12 00:00:00

  • Effects of peptide length and composition on binding to an empty class I MHC heterodimer.

    abstract::Class I major histocompatibility complex (MHC) proteins present peptide antigens to T cells during the immune response against viruses. Peptides are loaded into newly synthesized class I heterodimers in the endoplasmic reticulum such that most or all cell surface class I molecules contain peptides derived from endogen...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00192a020

    authors: Fahnestock ML,Johnson JL,Feldman RM,Tsomides TJ,Mayer J,Narhi LO,Bjorkman PJ

    更新日期:1994-07-05 00:00:00

  • Hemin inhibits ubiquitin-dependent proteolysis in both a higher plant and yeast.

    abstract::In eukaryotes, a major route for ATP-dependent protein breakdown proceeds through covalent intermediates of target proteins destined for degradation and the highly conserved, 76 amino acid protein ubiquitin. In rabbit reticulocytes, it has been shown that hemin effectively inhibits this pathway by blocking the catabol...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00409a025

    authors: Vierstra RD,Sullivan ML

    更新日期:1988-05-03 00:00:00

  • Role of the structural domain of troponin C in muscle regulation: NMR studies of Ca2+ binding and subsequent interactions with regions 1-40 and 96-115 of troponin I.

    abstract::The interaction between the calcium binding and inhibitory components of troponin is central to the regulation of muscle contraction. In this work, two-dimensional heteronuclear single-quantum coherence nuclear magnetic resonance (2D-¿1H,15N¿-HSQC NMR) spectroscopy was used to determine the stoichiometry, affinity, an...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi992579n

    authors: Mercier P,Li MX,Sykes BD

    更新日期:2000-03-21 00:00:00

  • Ion concentration and temperature dependence of DNA binding: comparison of PurR and LacI repressor proteins.

    abstract::Purine repressor (PurR) binding to specific DNA is enhanced by complexing with purines, whereas lactose repressor (LacI) binding is diminished by interaction with inducer sugars despite 30% identity in their protein sequences and highly homologous tertiary structures. Nonetheless, in switching from low- to high-affini...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi0028643

    authors: Moraitis MI,Xu H,Matthews KS

    更新日期:2001-07-10 00:00:00

  • Fate of the (2Fe-2S)(2+) cluster of Escherichia coli biotin synthase during reaction: a Mössbauer characterization.

    abstract::Biotin synthase, the enzyme which catalyzes the last step of the biosynthesis of biotin, contains only (2Fe-2S)(2+) clusters when isolated under aerobic conditions. Previous results showed that reduction by dithionite or photoreduced deazaflavin converts the (2Fe-2S)(2+) to (4Fe-4S)(2+,+). However, until now, no detai...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi034426c

    authors: Tse Sum Bui B,Benda R,Schünemann V,Florentin D,Trautwein AX,Marquet A

    更新日期:2003-07-29 00:00:00

  • Limited proteolysis and active-site labeling studies of soybean lipoxygenase.

    abstract::Soybean lipoxygenase 1 was studied using limited proteolysis and active-site labeling to begin the structural characterization of the enzyme in solution. The serine proteases trypsin and chymotrypsin cleaved the large monomeric protein (95 kDa) into two large polypeptides, a C-terminal fragment of about 30 kDa and an ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00148a034

    authors: Ramachandran S,Carroll RT,Dunham WR,Funk MO Jr

    更新日期:1992-08-25 00:00:00

  • NH3 Binding to the S2 State of the O2-Evolving Complex of Photosystem II: Analogue to H2O Binding during the S2 → S3 Transition.

    abstract::Ammonia binds directly to the oxygen-evolving complex of photosystem II (PSII) upon formation of the S2 intermediate, as evidenced by electron paramagnetic resonance spectroscopy. We explore the binding mode by using quantum mechanics/molecular mechanics methods and simulations of extended X-ray absorption fine struct...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.5b00974

    authors: Askerka M,Vinyard DJ,Brudvig GW,Batista VS

    更新日期:2015-09-29 00:00:00

  • Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of the effects of cholesterol in model systems.

    abstract::Deuterium nuclear magnetic resonance spectra of dimyristoylphosphatidylcholines specifically labeled in positions 2', 3', 4', 6', 8', 10', 12', and 14', of the 2 chain, of an N-deuteriomethylphosphatidylcholine, and of cholesterol-3alpha-d1, have been obtained by the Fourier transform method at 5.46 and 3.52 T on two ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00607a006

    authors: Oldfield E,Meadows M,Rice D,Jacobs R

    更新日期:1978-07-11 00:00:00

  • Reconstitution of membrane proteins. Spontaneous association of integral membrane proteins with preformed unilamellar lipid bilayers.

    abstract::We have developed a simple method for reconstituting pure, integral membrane proteins into phospholipid-protein vesicles. The method does not depend on use of detergents or sonication. It has been used successfully with three different types of integral membrane proteins: UDPglucuronosyltransferase (EC 2.4.1.17) from ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00336a040

    authors: Scotto AW,Zakim D

    更新日期:1985-07-16 00:00:00

  • Site-directed mutagenesis and 1H NMR spectroscopy of an interdomain segment in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

    abstract::Deletion of two of the three homologous lipoyl domains that form the N-terminal half of each dihydrolipoamide acetyltransferase (E2p) polypeptide chain of the Escherichia coli pyruvate dehydrogenase complex can be achieved by in vitro deletion in the structural gene aceF. A site-directed mutagenesis of this shortened ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00401a044

    authors: Texter FL,Radford SE,Laue ED,Perham RN,Miles JS,Guest JR

    更新日期:1988-01-12 00:00:00

  • Decoding protein-protein interactions through combinatorial chemistry: sequence specificity of SHP-1, SHP-2, and SHIP SH2 domains.

    abstract::A general, combinatorial library method for the rapid identification of high-affinity peptide ligands of protein modular domains is reported. The validity of this method has been demonstrated by determining the sequence specificity of four Src homology 2 (SH2) domains derived from protein tyrosine phosphatase SHP-1 an...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi051408h

    authors: Sweeney MC,Wavreille AS,Park J,Butchar JP,Tridandapani S,Pei D

    更新日期:2005-11-15 00:00:00

  • Interaction of an aromatic dibromoisothiouronium derivative with the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum.

    abstract::Isothiouronium compounds [Hoving, S., Bar-Shimon, M., Tijmes, J. J., Goldshleger, R., Tal, D. M., and Karlish, S. J. (1995) J. Biol. Chem. 270, 29788-29793] act as high-affinity competitive antagonists for Na(+) and K(+) (Rb(+)) on the renal Na(+)/K(+)-ATPase where they favor the E1 conformation. We have now character...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi026071n

    authors: Berman MC,Karlish SJ

    更新日期:2003-04-01 00:00:00

  • The stereoselectivity and catalytic properties of Xanthobacter autotrophicus 2-[(R)-2-Hydroxypropylthio]ethanesulfonate dehydrogenase are controlled by interactions between C-terminal arginine residues and the sulfonate of coenzyme M.

    abstract::2-[(R)-2-Hydroxypropylthio]ethanesulfonate (R-HPC) dehydrogenase (DH) catalyzes the reversible oxidation of R-HPC to 2-(2-ketopropylthio)ethanesulfonate (2-KPC) in a key reaction in the bacterial conversion of chiral epoxides to beta-keto acids. R-HPCDH is highly specific for the R-enantiomer of HPC, while a separate ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi049783h

    authors: Clark DD,Boyd JM,Ensign SA

    更新日期:2004-06-01 00:00:00

  • Using saturation-recovery EPR to measure distances in proteins: applications to photosystem II.

    abstract::The stable tyrosine radical YD. (tyrosine 160 in the D2 polypeptide) in photosystem II (PSII) exhibits nonexponential electron spin-lattice relaxation transients at low temperature. As previously reported, the tetranuclear Mn complex in PSII significantly enhances the spin-lattice relaxation of YD.. However, in Mn-dep...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00117a033

    authors: Hirsh DJ,Beck WF,Innes JB,Brudvig GW

    更新日期:1992-01-21 00:00:00

  • The very low- and intermediate-density lipoprotein fraction isolated from apolipoprotein E-knockout mice transforms macrophages to foam cells through an apolipoprotein E-independent pathway.

    abstract::Apolipoprotein E (apoE)-knockout mice develop severe atherosclerosis associated with high levels of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) in plasma. To investigate the atherogenic role of VLDL and IDL, the lipoprotein fraction containing both VLDL and IDL (apoEko-VLDL/IDL) was ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi980762v

    authors: Hakamata H,Sakaguchi H,Zhang C,Sakashita N,Suzuki H,Miyazaki A,Takeya M,Takahashi K,Kitamura N,Horiuchi S

    更新日期:1998-09-29 00:00:00

  • Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates.

    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

    authors: O'Brien G,Quinsey NS,Whisstock JC,Pike RN

    更新日期:2003-12-23 00:00:00