Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.

Abstract:

:The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Ponnuraj K,Xu Y,Macon K,Moore D,Volanakis JE,Narayana SV

doi

10.1016/s1097-2765(04)00160-1

subject

Has Abstract

pub_date

2004-04-09 00:00:00

pages

17-28

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(04)00160-1

journal_volume

14

pub_type

杂志文章
  • Identification of an mRNP complex regulating tumorigenesis at the translational elongation step.

    abstract::Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.02.003

    authors: Hussey GS,Chaudhury A,Dawson AE,Lindner DJ,Knudsen CR,Wilce MC,Merrick WC,Howe PH

    更新日期:2011-02-18 00:00:00

  • Finding DNA Ends within a Haystack of Chromatin.

    abstract::Identifying DNA fragile sites is crucial to reveal hotspots of genomic rearrangements, yet their precise mapping has been a challenge. A new study in this issue of Molecular Cell (Canela et al., 2016) introduces a highly sensitive and accurate method to detect DNA breaks in vivo that can be adapted to various experime...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2016.08.012

    authors: Banerjee U,Soutoglou E

    更新日期:2016-09-01 00:00:00

  • hnRNP A1 proofreads 3' splice site recognition by U2AF.

    abstract::One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays usin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.11.033

    authors: Tavanez JP,Madl T,Kooshapur H,Sattler M,Valcárcel J

    更新日期:2012-02-10 00:00:00

  • A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies.

    abstract::The transcriptional coactivators CBP and p300 are critical regulators of metazoan gene expression. They associate with many different DNA-bound transcription factors through small, conserved domains. We have identified a compactly folded 46 residue domain in CBP and p300, the IRF-3 binding domain (IBiD), and we have d...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00333-1

    authors: Lin CH,Hare BJ,Wagner G,Harrison SC,Maniatis T,Fraenkel E

    更新日期:2001-09-01 00:00:00

  • Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs.

    abstract::The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation, whereas FGF-10 pro...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.08.002

    authors: Francavilla C,Rigbolt KT,Emdal KB,Carraro G,Vernet E,Bekker-Jensen DB,Streicher W,Wikström M,Sundström M,Bellusci S,Cavallaro U,Blagoev B,Olsen JV

    更新日期:2013-09-26 00:00:00

  • Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence.

    abstract::S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenet...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.03.004

    authors: Haws SA,Yu D,Ye C,Wille CK,Nguyen LC,Krautkramer KA,Tomasiewicz JL,Yang SE,Miller BR,Liu WH,Igarashi K,Sridharan R,Tu BP,Cryns VL,Lamming DW,Denu JM

    更新日期:2020-04-16 00:00:00

  • DNA Breaks and End Resection Measured Genome-wide by End Sequencing.

    abstract::DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.06.034

    authors: Canela A,Sridharan S,Sciascia N,Tubbs A,Meltzer P,Sleckman BP,Nussenzweig A

    更新日期:2016-09-01 00:00:00

  • Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases.

    abstract::The S. cerevisiae SCFCdc4p ubiquitin-protein ligase complex promotes cell cycle transitions through degradation of cell cycle regulators. To investigate SCFCdc4p regulation in vivo, we examined the stability of individual SCFCdc4p components. Whereas Cdc53p and Skp1p were stable, Cdc4p, the F box-containing component ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80156-2

    authors: Zhou P,Howley PM

    更新日期:1998-11-01 00:00:00

  • A heterotrimeric PCNA in the hyperthermophilic archaeon Sulfolobus solfataricus.

    abstract::The sliding clamp, PCNA, of the archaeon Sulfolobus solfataricus P2 is a heterotrimer of three distinct subunits (PCNA1, 2, and 3) that assembles in a defined manner. The PCNA heterotrimer, but not individual subunits, stimulates the activities of the DNA polymerase, DNA ligase I, and the flap endonuclease (FEN1) of S...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00824-9

    authors: Dionne I,Nookala RK,Jackson SP,Doherty AJ,Bell SD

    更新日期:2003-01-01 00:00:00

  • Quantifying ubiquitin signaling.

    abstract::Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), including phosphorylation. Flux through such pathways is dictated by the fractional stoichiometry of distinct modifications and protein assemblies as well as the spatial organ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2015.02.020

    authors: Ordureau A,Münch C,Harper JW

    更新日期:2015-05-21 00:00:00

  • Genome-wide methylation profiles reveal quantitative views of human aging rates.

    abstract::The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.10.016

    authors: Hannum G,Guinney J,Zhao L,Zhang L,Hughes G,Sadda S,Klotzle B,Bibikova M,Fan JB,Gao Y,Deconde R,Chen M,Rajapakse I,Friend S,Ideker T,Zhang K

    更新日期:2013-01-24 00:00:00

  • Scd6 targets eIF4G to repress translation: RGG motif proteins as a class of eIF4G-binding proteins.

    abstract::The formation of mRNPs controls the interaction of the translation and degradation machinery with individual mRNAs. The yeast Scd6 protein and its orthologs regulate translation and mRNA degradation in yeast, C. elegans, D. melanogaster, and humans by an unknown mechanism. We demonstrate that Scd6 represses translatio...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.11.026

    authors: Rajyaguru P,She M,Parker R

    更新日期:2012-01-27 00:00:00

  • An Arginine Nexus in the RNA Polymerase II CTD.

    abstract::In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.12.013

    authors: Corden JL

    更新日期:2019-01-03 00:00:00

  • Liquid Active Zones for Controlling the Phases of Synaptic Transmission.

    abstract::Wu et al. (2019) establish that the active zone proteins RIM and RIM-BP undergo liquid-liquid phase separation to tether Ca2+ channels. This important finding sets a new framework to study assembly and function of the presynaptic nerve terminal. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2019.02.020

    authors: Emperador-Melero J,Kaeser PS

    更新日期:2019-03-07 00:00:00

  • Mitotic wnt signaling promotes protein stabilization and regulates cell size.

    abstract::Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing β-catenin-dependent transcription of target genes. In proliferating cells Wnt signaling peaks in the G2/M phase of the cell cycle, but the significance of this "mitotic Wnt signaling" is unclear. Here we introduce Wnt-dependent stabilizati...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.04.014

    authors: Acebron SP,Karaulanov E,Berger BS,Huang YL,Niehrs C

    更新日期:2014-05-22 00:00:00

  • Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex.

    abstract::The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.05.028

    authors: Kowalinski E,Kögel A,Ebert J,Reichelt P,Stegmann E,Habermann B,Conti E

    更新日期:2016-07-07 00:00:00

  • Mammalian mirtron genes.

    abstract::Mirtrons are alternative precursors for microRNA biogenesis that were recently described in invertebrates. These short hairpin introns use splicing to bypass Drosha cleavage, which is otherwise essential for the generation of canonical animal microRNAs. Using computational and experimental strategies, we now establish...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.09.028

    authors: Berezikov E,Chung WJ,Willis J,Cuppen E,Lai EC

    更新日期:2007-10-26 00:00:00

  • Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.

    abstract::Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with hom...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00465-3

    authors: Mullen MM,Haan KM,Longnecker R,Jardetzky TS

    更新日期:2002-02-01 00:00:00

  • Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIα and PKCδ signaling.

    abstract::BIK protein is an initiator of mitochondrial apoptosis, and BIK expression is induced by proapoptotic signals, including DNA damage. Here, we demonstrate that 3' end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P(2)-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKC...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.11.017

    authors: Li W,Laishram RS,Ji Z,Barlow CA,Tian B,Anderson RA

    更新日期:2012-01-13 00:00:00

  • Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.

    abstract::Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue lo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.11.013

    authors: Chen C,Ha BH,Thévenin AF,Lou HJ,Zhang R,Yip KY,Peterson JR,Gerstein M,Kim PM,Filippakopoulos P,Knapp S,Boggon TJ,Turk BE

    更新日期:2014-01-09 00:00:00

  • E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1.

    abstract::Ubiquitination typically occurs through the sequential action of three enzymes catalyzing ubiquitin activation (E1), conjugation (E2), and ligation (E3) and regulates diverse eukaryotic cellular processes. Although monoubiquitination commonly confers nondegradative activities, mechanisms underlying its temporal and sp...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.04.022

    authors: Sun L,Fang J

    更新日期:2016-06-16 00:00:00

  • Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes.

    abstract::Nucleosome loss from a promoter region has recently been described as a potential mechanism for transcriptional regulation. We investigated whether H3/H4 histone chaperones mediate the loss of nucleosomes from the promoter of the yeast PHO5 gene during transcriptional activation. We found that antisilencing function 1...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.05.016

    authors: Adkins MW,Howar SR,Tyler JK

    更新日期:2004-06-04 00:00:00

  • Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1.

    abstract::In yeast, histone H3/H4 exchange independent of replication is poorly understood. Here, we analyzed the deposition of histone H3 molecules, synthesized during G1, using a high-density microarray histone exchange assay. While we found that H3 exchange in coding regions requires high levels of transcription, promoters e...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.07.011

    authors: Rufiange A,Jacques PE,Bhat W,Robert F,Nourani A

    更新日期:2007-08-03 00:00:00

  • Arginine methylation modulates autophagic degradation of PGL granules in C. elegans.

    abstract::The selective degradation of intracellular components by autophagy involves sequential interactions of the cargo with a receptor, which also binds the autophagosomal protein Atg8 and a scaffold protein. Here, we demonstrated that mutations in C. elegans epg-11, which encodes an arginine methyltransferase homologous to...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.09.014

    authors: Li S,Yang P,Tian E,Zhang H

    更新日期:2013-11-07 00:00:00

  • RNA editing-associated protein 1 is an RNA binding protein with specificity for preedited mRNA.

    abstract::RNA editing in the mitochondria of kinetoplastids involves the addition and deletion of uridines at specific sites as directed by guide RNAs (gRNAs). Ample evidence shows that ribonucleoprotein (RNP) complexes carry out this posttranscriptional processing. One component of RNA editing complexes is REAP-1, a protein of...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00231-3

    authors: Madison-Antenucci S,Hajduk SL

    更新日期:2001-04-01 00:00:00

  • pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities.

    abstract::The interaction between pRB and E2F is critical for control of the cell cycle and apoptosis. Here we report that pRB contains two distinct E2F binding sites. The previously identified E2F binding site on pRB is necessary for stable association with E2Fs on DNA. A second E2F interaction site is located entirely within ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00344-7

    authors: Dick FA,Dyson N

    更新日期:2003-09-01 00:00:00

  • Protein disulfide isomerase A6 controls the decay of IRE1α signaling via disulfide-dependent association.

    abstract::The response to endoplasmic reticulum (ER) stress relies on activation of unfolded protein response (UPR) sensors, and the outcome of the UPR depends on the duration and strength of signal. Here, we demonstrate a mechanism that attenuates the activity of the UPR sensor inositol-requiring enzyme 1α (IRE1α). A resident ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.01.004

    authors: Eletto D,Eletto D,Dersh D,Gidalevitz T,Argon Y

    更新日期:2014-02-20 00:00:00

  • General and versatile autoinhibition of PLC isozymes.

    abstract::Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.06.018

    authors: Hicks SN,Jezyk MR,Gershburg S,Seifert JP,Harden TK,Sondek J

    更新日期:2008-08-08 00:00:00

  • Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release.

    abstract::Peptide release on the ribosome is catalyzed in the large subunit peptidyl transferase center by release factors on recognition of stop codons in the small subunit decoding center. Here we examine the role of the decoding center in this process. Mutation of decoding center nucleotides or removal of 2'OH groups from th...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.09.015

    authors: Youngman EM,He SL,Nikstad LJ,Green R

    更新日期:2007-11-30 00:00:00

  • ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.

    abstract::Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechan...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.04.021

    authors: Turakhiya A,Meyer SR,Marincola G,Böhm S,Vanselow JT,Schlosser A,Hofmann K,Buchberger A

    更新日期:2018-06-07 00:00:00