Locavore science - p453

doi:10.1038/nsmb0509-453

As we set off into the full swing of traveling for the globally oriented meeting season, it's worth also remembering the delights of local science consumption.

Full Text - Locavore science | PDF (216 KB) - Locavore science

Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA - pp454 - 455

Linda Chelico, Phuong Pham & Myron F Goodman

doi:10.1038/nsmb0509-454

Full Text - Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA | PDF (97 KB) - Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA

Reply to "Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA" - pp455 - 456

Roni Nowarski, Elena Britan-Rosich & Moshe Kotler

doi:10.1038/nsmb0509-455

Full Text - Reply to "Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA" | PDF (89 KB) - Reply to "Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA"

Nuclear transport comes full circle - pp457 - 459

Erik W Debler, Günter Blobel & André Hoelz

doi:10.1038/nsmb0509-457

Previous structural snapshots of snurportin have provided insights into its cargo recognition and nuclear import. The structure of snurportin bound to its export factor CRM1 now reveals the molecular basis of its recycling back into the cytoplasm, illuminating general principles of nuclear export sequence recognition.

Full Text - Nuclear transport comes full circle | PDF (1,345 KB) - Nuclear transport comes full circle

See also: Brief Communication by Dong et al.

Going round in circles: the structural biology of type III secretion systems - pp459 - 460

Gabriel Waksman

doi:10.1038/nsmb0509-459

Type III secretions systems (T3SSs) are major bacterial virulence factors responsible for secretion and injection of protein effectors into host cells. New structures illuminate their ring structure and identify novel ring-mediating structural scaffolds.

Full Text - Going round in circles: the structural biology of type III secretion systems | PDF (253 KB) - Going round in circles: the structural biology of type III secretion systems

See also: Article by Spreter et al. | Article by Hodgkinson et al.

Research highlights - p461

doi:10.1038/nsmb0509-461

Full Text - Research highlights | PDF (147 KB) - Research highlights

Metabolism control by the circadian clock and vice versa - pp462 - 467

Kristin Eckel-Mahan & Paolo Sassone-Corsi

doi:10.1038/nsmb.1595

Abstract - | Full Text - Metabolism control by the circadian clock and vice versa | PDF (368 KB) - Metabolism control by the circadian clock and vice versa

A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system - pp468 - 476

Thomas Spreter, Calvin K Yip, Sarah Sanowar, Ingemar André, Tyler G Kimbrough, Marija Vuckovic, Richard A Pfuetzner, Wanyin Deng, Angel C Yu, B Brett Finlay, David Baker, Samuel I Miller & Natalie C J Strynadka

doi:10.1038/nsmb.1603

• PDB code

  • 3GR5
  • 3GR0
  • 3GR1

• 3D view

  • 3GR5
  • 3GR0
  • 3GR1

The type III secretion system (T3SS) of pathogenic bacteria is composed of a series of rings in the inner and outer bacterial membranes. Crystallographic studies of EscJ and PrgH, proteins that comprise the two inner membrane rings of the T3SS, suggest that a conserved structural motif serves as a platform for ring assembly. Additional docking and modeling studies reveal details of the T3SS architecture and assembly.

Abstract - | Full Text - A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system | PDF (973 KB) - A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system | Supplementary information

See also: News and Views by Waksman

Three-dimensional reconstruction of the Shigella T3SS transmembrane regions reveals 12-fold symmetry and novel features throughout - pp477 - 485

Julie L Hodgkinson, Ashley Horsley, David Stabat, Martha Simon, Steven Johnson, Paula C A da Fonseca, Edward P Morris, Joseph S Wall, Susan M Lea & Ariel J Blocker

doi:10.1038/nsmb.1599

Gram-negative bacteria use type III secretion systems (T3SSs) to pass virulence factors into host cells, making them potential therapeutic targets to combat bacterial infection. A new EM study of the needle complex from the Shigella T3SS reveals 12-fold symmetry throughout and suggests interactions important for self-assembly and complex stability.

Abstract - | Full Text - Three-dimensional reconstruction of the Shigella T3SS transmembrane regions reveals 12-fold symmetry and novel features throughout | PDF (964 KB) - Three-dimensional reconstruction of the Shigella T3SS transmembrane regions reveals 12-fold symmetry and novel features throughout | Supplementary information

See also: News and Views by Waksman

Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains - pp486 - 491

Chi-kong Lau, Jennifer L Bachorik & Gideon Dreyfuss

doi:10.1038/nsmb.1584

Gemin5 is a WD repeat protein that binds small nuclear RNAs (snRNAs) through a specific sequence in the context of the SMN complex, a function required for spliceosomal snRNP biogenesis. Reduced levels of SMN cause spinal muscular atrophy. A series of biochemical experiments now indicate that the WD repeat region of Gemin5 recognizes the snRNAs in a sequence-specific fashion, suggesting that WD repeats are capable of RNA binding.

Abstract - | Full Text - Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains | PDF (613 KB) - Gemin5-snRNA interaction reveals an RNA binding function for WD repeat domains | Supplementary information

miR-24–mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells - pp492 - 498

Ashish Lal, Yunfeng Pan, Francisco Navarro, Derek M Dykxhoorn, Lisa Moreau, Eti Meire, Zvi Bentwich, Judy Lieberman & Dipanjan Chowdhury

doi:10.1038/nsmb.1589

Most terminally differentiated cells have a diminished capacity to respond to and repair DNA damage. Now a microRNA is shown to have a role in this phenotype in blood cells: miR-24 is upregulated in blood cells differentiated in vitro and decreases the levels of H2AX, a histone variant with a key role in the response to DNA double-stranded breaks.

Abstract - | Full Text - miR-24–mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells | PDF (600 KB) - miR-24–mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells | Supplementary information

Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis - pp499 - 508

Fang Fang Yin, Scott Bailey, C Axel Innis, Mihai Ciubotaru, Satwik Kamtekar, Thomas A Steitz & David G Schatz

doi:10.1038/nsmb.1593

• PDB code

  • 3GNA
  • 3GNB

• 3D view

  • 3GNA
  • 3GNB

V(D)J recombination is mediated by the products of the recombination activation genes, RAG1 and RAG2. DNA binding and cleavage are targeted by recombination sequences that flank each gene segment and are composed of well-conserved heptamer and nonamer sequences separated either by 12 or 23 base pairs. Schatz and co-workers report the crystal structure of the RAG1 nonamer binding domain (NBD) bound to its cognate sequence. The NBD adopts an intertwined dimer that mediates the synapsis of two DNA molecules. Biochemical and FRET experiments support the structural findings and have implications for the regulation of DNA binding and cleavage by RAG1/2.

Abstract - | Full Text - Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis | PDF (1,142 KB) - Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis | Supplementary information

Molecular mimicry of SUMO promotes DNA repair - pp509 - 516

John Prudden, J Jefferson P Perry, Andrew S Arvai, John A Tainer & Michael N Boddy

doi:10.1038/nsmb.1582

• PDB code

  • 3GOE

• 3D view

  • 3GOE

Dysfunction of SUMO or Rad60 causes overlapping phenotypes that include genomic instability. Now, a nonsubstrate interaction between SUMO-like domain 2 (SLD2) of Rad60 and the SUMO-conjugating enzyme Ubc9 is shown to suppress aberrant replication-associated homologous recombination. Thus, SUMO mimicry provides critical regulation in the SUMO pathway.

Abstract - | Full Text - Molecular mimicry of SUMO promotes DNA repair | PDF (632 KB) - Molecular mimicry of SUMO promotes DNA repair | Supplementary information

Active nuclear import and cytoplasmic retention of activation-induced deaminase - pp517 - 527

Anne-Marie Patenaude, Alexandre Orthwein, Yi Hu, Vanina A Campo, Bodil Kavli, Alejandro Buschiazzo & Javier M Di Noia

doi:10.1038/nsmb.1598

The enzyme activation-induced deaminase (AID) promotes antibody diversification after B-cell activation, by causing mutagenic lesions on DNA. Hence, AID's actions must be tightly controlled. AID is found mainly in the cytosolic compartment and contains a known nuclear export sequence. Now a structural nuclear localization sequence and a cytosolic-retention determinant are identified in AID and found to have a role in localization and function.

Abstract - | Full Text - Active nuclear import and cytoplasmic retention of activation-induced deaminase | PDF (1,166 KB) - Active nuclear import and cytoplasmic retention of activation-induced deaminase | Supplementary information

Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome - pp528 - 533

Rebecca M Voorhees, Albert Weixlbaumer, David Loakes, Ann C Kelley & V Ramakrishnan

doi:10.1038/nsmb.1577

• PDB code

  • 2WDK
  • 2WDL
  • 2WDM
  • 2WDN
  • 2WDG
  • 2WDH
  • 2WDI
  • 2WDJ

• 3D view

  • 2WDK
  • 2WDL
  • 2WDM
  • 2WDN
  • 2WDG
  • 2WDH
  • 2WDI
  • 2WDJ

Protein synthesis is catalyzed in the peptidyl transferase center of the ribosome. The structure of the 70S ribosome containing tRNAs now gives insight into the active site of a complete ribosome and reveals a direct interaction between the tRNA substrate and ribosomal proteins.

Abstract - | Full Text - Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome | PDF (684 KB) - Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome | Supplementary information

Single-molecule force spectroscopy reveals a highly compliant helical folding for the 30-nm chromatin fiber - pp534 - 540

Maarten Kruithof, Fan-Tso Chien, Andrew Routh, Colin Logie, Daniela Rhodes & John van Noort

doi:10.1038/nsmb.1590

In eukaryotic cells, DNA is wrapped around histones to form nucleosomes, which are further organized into the 30-nm chromatin fiber. A single-molecule study with homogeneous chromatin fibers now shows that the chromatin fiber behaves as a simple spring, stretching up to three times in response to pulling, a behavior indicative of a one-start helix structure. Linker histones stabilize the fiber but do not make it stiffer.

Abstract - | Full Text - Single-molecule force spectroscopy reveals a highly compliant helical folding for the 30-nm chromatin fiber | PDF (552 KB) - Single-molecule force spectroscopy reveals a highly compliant helical folding for the 30-nm chromatin fiber | Supplementary information

A plant 5S ribosomal RNA mimic regulates alternative splicing of transcription factor IIIA pre-mRNAs - pp541 - 549

Ming C Hammond, Andreas Wachter & Ronald R Breaker

doi:10.1038/nsmb.1588

Production of complex machines such as the ribosome requires coordinated regulation of the components. A widely conserved plant regulator of alternative splicing on the TFIIIA transcription factor mRNA has been found. The RNA structurally mimics the 5S rRNA and, accordingly, binds ribosomal protein L5, which thus affects splicing and production of TFIIIA. As TFIIIA is needed for transcription of the 5S rRNA, this work defines a regulatory circuit for coordinating 5S rRNA production by its binding protein.

Abstract - | Full Text - A plant 5S ribosomal RNA mimic regulates alternative splicing of transcription factor IIIA pre-mRNAs | PDF (756 KB) - A plant 5S ribosomal RNA mimic regulates alternative splicing of transcription factor IIIA pre-mRNAs | Supplementary information

The nucleotide binding dynamics of human MSH2–MSH3 are lesion dependent - pp550 - 557

Barbara A L Owen, Walter H Lang & Cynthia T McMurray

doi:10.1038/nsmb.1596

The Msh2–Msh3 complex recognizes DNA mismatch lesions, with stronger affinity for small insertion and deletion loops. Now the nucleotide binding properties of Msh2–Msh3 are studied, revealing the changes upon binding to DNA molecules with a loop lesion, indicating how this mismatch sensor can signal the repair machinery.

Abstract - | Full Text - The nucleotide binding dynamics of human MSH2–MSH3 are lesion dependent | PDF (685 KB) - The nucleotide binding dynamics of human MSH2–MSH3 are lesion dependent | Supplementary information

Structural basis for assembly and disassembly of the CRM1 nuclear export complex - pp558 - 560

Xiuhua Dong, Anindita Biswas & Yuh Min Chook

doi:10.1038/nsmb.1586

The nuclear transport receptor CRM1 mediates protein export from the nucleus through recognition of leucine-rich nuclear export signals on substrates. Structural analysis, based in part on the recent structure of a CRM1-SNUPN complex, reveal determinants for substrate binding and suggest a mechanism for binding partner-assisted dissociation of SNUPN in the cytoplasm.

Abstract - | Full Text - Structural basis for assembly and disassembly of the CRM1 nuclear export complex | PDF (612 KB) - Structural basis for assembly and disassembly of the CRM1 nuclear export complex | Supplementary information

See also: News and Views by Debler et al.

The WAVE regulatory complex is inhibited - pp561 - 563

Ayman M Ismail, Shae B Padrick, Baoyu Chen, Junko Umetani & Michael K Rosen

doi:10.1038/nsmb.1587

WAVE proteins in the WASP family are controlled by incorporation into the WAVE regulatory complex (WRC), which transmits information from the Rac GTPase to the actin cytoskeleton. By reconstituting human and fly WRCs, the native complex is shown to be inactive. Rac activates the WRC, but does not cause subunit dissociation. These results reconcile previous work and reveal common regulatory principles for the WASP family.

Abstract - | Full Text - The WAVE regulatory complex is inhibited | PDF (874 KB) - The WAVE regulatory complex is inhibited | Supplementary information

Developmental programming of CpG island methylation profiles in the human genome - pp564 - 571

Ravid Straussman, Deborah Nejman, Douglas Roberts, Israel Steinfeld, Barak Blum, Nissim Benvenisty, Itamar Simon, Zohar Yakhini & Howard Cedar

doi:10.1038/nsmb.1594

A genome-wide analysis of methylated DNA from human embryonic stem cells and adult tissues provides a comprehensive view of unmethylated regions and leads to the identification of sequence motifs that can predict whether a region escapes de novo methylation. This algorithm is used to identify novel, non-CpG unmethylated regions, including intragenic and tissue-specific ones.

Abstract - | Full Text - Developmental programming of CpG island methylation profiles in the human genome | PDF (760 KB) - Developmental programming of CpG island methylation profiles in the human genome | Supplementary information

Corrigendum: Telomere protection by mammalian Pot1 requires interaction with Tpp1 - p572

Dirk Hockemeyer, Wilhelm Palm, Tobias Else, Jan-Peter Daniels, Kaori K Takai, Jeffrey Z-S Ye, Catherine E Keegan, Titia de Lange & Gary D Hammer

doi:10.1038/nsmb0509-572a

Full Text - Corrigendum: Telomere protection by mammalian Pot1 requires interaction with Tpp1 | PDF (73 KB) - Corrigendum: Telomere protection by mammalian Pot1 requires interaction with Tpp1

Corrigendum: Integration of an electric-metal sensory experience in the Slo1 BK channel - p572

Frank T Horrigan & Toshinori Hoshi

doi:10.1038/nsmb0509-572b

Full Text - Corrigendum: Integration of an electric-metal sensory experience in the Slo1 BK channel | PDF (73 KB) - Corrigendum: Integration of an electric-metal sensory experience in the Slo1 BK channel