Nature Structural & Molecular Biology An integrated forum for structural and molecular studies. http://www.nature.com/nsmb/current_issue/ Nature Publishing Group en © 2009 Nature Publishing Group Nature Structural & Molecular Biology 1545-9993 1545-9985 © 2009 Nature Publishing Group permissions@nature.com Nature Structural & Molecular Biology http://www.nature.com/includes/rj_globnavimages/nsmb_logo.gif http://www.nature.com/nsmb/ Welcoming the best and the brightest from everywhere http://dx.doi.org/10.1038/nsmb0709-677 The US State Department promises to accelerate the visa process for foreign graduate students and postdoctoral researchers. That will be a welcome change. Welcoming the best and the brightest from everywhere

Nature Structural & Molecular Biology 16, 677 (2009). doi:10.1038/nsmb0709-677

The US State Department promises to accelerate the visa process for foreign graduate students and postdoctoral researchers. That will be a welcome change.

]]> Welcoming the best and the brightest from everywhere doi:10.1038/nsmb0709-677 Nature Structural & Molecular Biology 16, 677 (2009) Nature Structural & Molecular Biology 16 7 Editorial 677 677 WDR5, a complexed protein http://dx.doi.org/10.1038/nsmb0709-678 The WD40 protein WDR5 is a core subunit of the human MLL and SET1 (hCOMPASS) histone H3 Lys4 (H3K4) methyltransferase complexes. Although initial studies suggested that WDR5 interacts with methylated H3K4 to catalyze Lys4 trimethylation, recent work has revealed that it binds an arginine-bearing motif in MLL1, promoting complex assembly and activity. These findings suggest that WDR5 functions as a peptidyl arginine–recognition factor that facilitates the assembly of hCOMPASS and other chromatin-modifying complexes. WDR5, a complexed protein

Nature Structural & Molecular Biology 16, 678 (2009). doi:10.1038/nsmb0709-678

Authors: Raymond C Trievel & Ali Shilatifard

The WD40 protein WDR5 is a core subunit of the human MLL and SET1 (hCOMPASS) histone H3 Lys4 (H3K4) methyltransferase complexes. Although initial studies suggested that WDR5 interacts with methylated H3K4 to catalyze Lys4 trimethylation, recent work has revealed that it binds an arginine-bearing motif in MLL1, promoting complex assembly and activity. These findings suggest that WDR5 functions as a peptidyl arginine–recognition factor that facilitates the assembly of hCOMPASS and other chromatin-modifying complexes.

]]> WDR5, a complexed protein Raymond C Trievel Ali Shilatifard doi:10.1038/nsmb0709-678 Nature Structural & Molecular Biology 16, 678 (2009) Nature Structural & Molecular Biology 16 7 Commentary 678 680 Energetics of protein hydrogen bonds http://dx.doi.org/10.1038/nsmb0709-681 In this issue, an article gives insight into the microenvironment's influence on the contribution of hydrogen bonds to protein stability. Energetics of protein hydrogen bonds

Nature Structural & Molecular Biology 16, 681 (2009). doi:10.1038/nsmb0709-681

Author: C Nick Pace

In this issue, an article gives insight into the microenvironment's influence on the contribution of hydrogen bonds to protein stability.

]]> Energetics of protein hydrogen bonds C Nick Pace doi:10.1038/nsmb0709-681 Nature Structural & Molecular Biology 16, 681 (2009) Nature Structural & Molecular Biology 16 7 News and Views 681 682 Research highlights http://dx.doi.org/10.1038/nsmb0709-683 Research highlights

Nature Structural & Molecular Biology 16, 683 (2009). doi:10.1038/nsmb0709-683

]]> Research highlights doi:10.1038/nsmb0709-683 Nature Structural & Molecular Biology 16, 683 (2009) Nature Structural & Molecular Biology 16 7 Research Highlights 683 683 Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins http://dx.doi.org/10.1038/nsmb.1610 The contribution of hydrogen bonding to the thermodynamics of protein folding is not well understood. The strength of hydrogen bonds is now found to depend on the polarity of their microenvironment, being stronger in non-polar surroundings. Thus, the burial or solvent exposure of a few hydrogen bonds near the surface of a protein can significantly stabilize or destabilize its native state. Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins

Nature Structural & Molecular Biology 16, 684 (2009). doi:10.1038/nsmb.1610

Authors: Jianmin Gao, Daryl A Bosco, Evan T Powers & Jeffery W Kelly

]]> Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins Jianmin Gao Daryl A Bosco Evan T Powers Jeffery W Kelly doi:10.1038/nsmb.1610 Nature Structural & Molecular Biology 16, 684 (2009) 2009-06-14 Nature Structural & Molecular Biology 2009-06-14 16 7 Article 684 690 The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling http://dx.doi.org/10.1038/nsmb.1632 Hedgehog (Hh) proteins are involved in multiple developmental processes. Hedgehog-interacting proteins (Hhips) bind and inhibit vertebrate Hh proteins. A structure of HHIP in complex with human SHH now shows a distinct binding site from previous ligand structures, with the pseudocatalytic site having a key role in binding. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling

Nature Structural & Molecular Biology 16, 691 (2009). doi:10.1038/nsmb.1632

Authors: Ivan Bosanac, Henry R Maun, Suzie J Scales, Xiaohui Wen, Andreas Lingel, J Fernando Bazan, Frederic J de Sauvage, Sarah G Hymowitz & Robert A Lazarus

]]> The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling Ivan Bosanac Henry R Maun Suzie J Scales Xiaohui Wen Andreas Lingel J Fernando Bazan Frederic J de Sauvage Sarah G Hymowitz Robert A Lazarus doi:10.1038/nsmb.1632 Nature Structural & Molecular Biology 16, 691 (2009) 2009-06-28 Nature Structural & Molecular Biology 2009-06-28 16 7 Article 691 697 Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP http://dx.doi.org/10.1038/nsmb.1607 Hedgehog (Hh) signaling molecules are involved in multiple developmental processes. Hedgehog-interacting protein (Hhip) binds and inhibits vertebrate Hh proteins. Structures of HHIP in complex with SHH and DHH now show a distinct binding site from previous ligand structures, with metal-binding sites having a role in interaction. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP

Nature Structural & Molecular Biology 16, 698 (2009). doi:10.1038/nsmb.1607

Authors: Benjamin Bishop, A Radu Aricescu, Karl Harlos, Chris A O'Callaghan, E Yvonne Jones & Christian Siebold

]]> Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP Benjamin Bishop A Radu Aricescu Karl Harlos Chris A O'Callaghan E Yvonne Jones Christian Siebold doi:10.1038/nsmb.1607 Nature Structural & Molecular Biology 16, 698 (2009) 2009-06-28 Nature Structural & Molecular Biology 2009-06-28 16 7 Article 698 703 Structural determinants of gating in the TRPV1 channel http://dx.doi.org/10.1038/nsmb.1633 Transient receptor potential channels are involved in sensory perception, and TRPV1 is a sensor of burning pain signals and can be modulated by acidic pH, capsaicin and heat. Substituted cysteine accessibility is used to probe state-dependent structural arrangements of the presumed pore-lining S6 helix, revealing two constrictions that participate in gating activity of the channel pore. Structural determinants of gating in the TRPV1 channel

Nature Structural & Molecular Biology 16, 704 (2009). doi:10.1038/nsmb.1633

Authors: Héctor Salazar, Andrés Jara-Oseguera, Enrique Hernández-García, Itzel Llorente, Imilla I Arias-Olguín, Manuel Soriano-García, León D Islas & Tamara Rosenbaum

]]> Structural determinants of gating in the TRPV1 channel Héctor Salazar Andrés Jara-Oseguera Enrique Hernández-García Itzel Llorente Imilla I Arias-Olguín Manuel Soriano-García León D Islas Tamara Rosenbaum doi:10.1038/nsmb.1633 Nature Structural & Molecular Biology 16, 704 (2009) 2009-06-28 Nature Structural & Molecular Biology 2009-06-28 16 7 Article 704 710 The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states http://dx.doi.org/10.1038/nsmb.1616 Telomeres alternate between telomerase-extendable and telomerase-unextendable states. Now this switch is reconstituted in vitro, using DNA templates and purified telomeric proteins from yeast. The molecular chaperone Hsp82 is shown to have a role in this switch by modulating the DNA binding activity of Cdc13. The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states

Nature Structural & Molecular Biology 16, 711 (2009). doi:10.1038/nsmb.1616

Authors: Diane C DeZwaan, Oyetunji A Toogun, Frank J Echtenkamp & Brian C Freeman

]]> The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states Diane C DeZwaan Oyetunji A Toogun Frank J Echtenkamp Brian C Freeman doi:10.1038/nsmb.1616 Nature Structural & Molecular Biology 16, 711 (2009) 2009-06-14 Nature Structural & Molecular Biology 2009-06-14 16 7 Article 711 716 Control of alternative splicing through siRNA-mediated transcriptional gene silencing http://dx.doi.org/10.1038/nsmb.1620 Exogenously applied small RNAs have previously been shown to inhibit transcriptional levels when targeted to promoters. They are now shown to alter the ratio of alternative splice forms. The features of splice form alteration are reminiscent of transcriptional gene silencing by siRNAs. Control of alternative splicing through siRNA-mediated transcriptional gene silencing

Nature Structural & Molecular Biology 16, 717 (2009). doi:10.1038/nsmb.1620

Authors: Mariano Alló, Valeria Buggiano, Juan P Fededa, Ezequiel Petrillo, Ignacio Schor, Manuel de la Mata, Eneritz Agirre, Mireya Plass, Eduardo Eyras, Sherif Abou Elela, Roscoe Klinck, Benoit Chabot & Alberto R Kornblihtt

]]> Control of alternative splicing through siRNA-mediated transcriptional gene silencing Mariano Alló Valeria Buggiano Juan P Fededa Ezequiel Petrillo Ignacio Schor Manuel de la Mata Eneritz Agirre Mireya Plass Eduardo Eyras Sherif Abou Elela Roscoe Klinck Benoit Chabot Alberto R Kornblihtt doi:10.1038/nsmb.1620 Nature Structural & Molecular Biology 16, 717 (2009) 2009-06-21 Nature Structural & Molecular Biology 2009-06-21 16 7 Article 717 724 Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen http://dx.doi.org/10.1038/nsmb.1619 The lamprey adaptive immune system is evolutionarily distinct from ours and based on recognition by leucine-rich repeat proteins rather than antibodies. The crystal structure of a lamprey variable lymphocyte receptor in complex with a protein antigen now gives insight into how a distinct adaptive immune molecule recognizes a protein antigen. Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen

Nature Structural & Molecular Biology 16, 725 (2009). doi:10.1038/nsmb.1619

Authors: C Alejandro Velikovsky, Lu Deng, Satoshi Tasumi, Lakshminarayan M Iyer, Melissa C Kerzic, L Aravind, Zeev Pancer & Roy A Mariuzza

]]> Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen C Alejandro Velikovsky Lu Deng Satoshi Tasumi Lakshminarayan M Iyer Melissa C Kerzic L Aravind Zeev Pancer Roy A Mariuzza doi:10.1038/nsmb.1619 Nature Structural & Molecular Biology 16, 725 (2009) 2009-06-21 Nature Structural & Molecular Biology 2009-06-21 16 7 Article 725 730 Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2 http://dx.doi.org/10.1038/nsmb.1625 The Brr2 ATPase is a large DExD/H-box helicase required for key snRNA-remodeling steps during the splicing reaction. The structure of part of Brr2, in conjunction with modeling and functional analysis, indicates that it probably resembles the Hel308 DNA helicase and may share a similar helicase mechanism. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2

Nature Structural & Molecular Biology 16, 731 (2009). doi:10.1038/nsmb.1625

Authors: Lingdi Zhang, Tao Xu, Corina Maeder, Laura-Oana Bud, James Shanks, Jay Nix, Christine Guthrie, Jeffrey A Pleiss & Rui Zhao

]]> Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2 Lingdi Zhang Tao Xu Corina Maeder Laura-Oana Bud James Shanks Jay Nix Christine Guthrie Jeffrey A Pleiss Rui Zhao doi:10.1038/nsmb.1625 Nature Structural & Molecular Biology 16, 731 (2009) 2009-06-14 Nature Structural & Molecular Biology 2009-06-14 16 7 Article 731 739 Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA http://dx.doi.org/10.1038/nsmb.1624 The box H/ACA pseudouridine synthase complex guides modification of small nucleolar and Cajal body ribonucleoproteins (sno/scaRNAs), which are essential for maturation of the ribosome and spliceosome. The structure of a functional H/ACA complex containing L7Ae, Nop1 and Cbf5 proteins bound to the substrate and guide RNAs and with a catalytically rearranged substrate in the active site is now presented. Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA

Nature Structural & Molecular Biology 16, 740 (2009). doi:10.1038/nsmb.1624

Authors: Bo Liang, Jing Zhou, Elliot Kahen, Rebecca M Terns, Michael P Terns & Hong Li

]]> Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA Bo Liang Jing Zhou Elliot Kahen Rebecca M Terns Michael P Terns Hong Li doi:10.1038/nsmb.1624 Nature Structural & Molecular Biology 16, 740 (2009) 2009-05-28 Nature Structural & Molecular Biology 2009-05-28 16 7 Article 740 746 A UPF3-mediated regulatory switch that maintains RNA surveillance http://dx.doi.org/10.1038/nsmb.1612 Nonsense-mediated decay is a surveillance pathway that removes transcripts containing a premature stop codon. UPF3 is unusual among the trans-acting factors in the pathway because there are two distinct homologs, UPF3A and UPF3B. Given that patients with reduced UPF3B contain upregulated levels of UPF3A, a regulatory interplay between the two factors is uncovered, where competition for UPF2 binding destabilizes the unbound factor. A UPF3-mediated regulatory switch that maintains RNA surveillance

Nature Structural & Molecular Biology 16, 747 (2009). doi:10.1038/nsmb.1612

Authors: Wai-Kin Chan, Angela D Bhalla, Hervé Le Hir, Lam Son Nguyen, Lulu Huang, Jozef Gécz & Miles F Wilkinson

]]> A UPF3-mediated regulatory switch that maintains RNA surveillance Wai-Kin Chan Angela D Bhalla Hervé Le Hir Lam Son Nguyen Lulu Huang Jozef Gécz Miles F Wilkinson doi:10.1038/nsmb.1612 Nature Structural & Molecular Biology 16, 747 (2009) 2009-06-07 Nature Structural & Molecular Biology 2009-06-07 16 7 Article 747 753 Structural basis for ESCRT-III protein autoinhibition http://dx.doi.org/10.1038/nsmb.1621 ESCRT-III proteins play important roles in multivesicular body (MVB) formation, cytokinesis, and enveloped virus budding. The structure of Ist1, which also functions in cytokinesis and MVB sorting, reveals that it, too, is an ESCRT-III family member and suggests that this protein family uses a common mode of autoinhibition. Structural basis for ESCRT-III protein autoinhibition

Nature Structural & Molecular Biology 16, 754 (2009). doi:10.1038/nsmb.1621

Authors: Monika Bajorek, Heidi L Schubert, John McCullough, Charles Langelier, Debra M Eckert, William-May B Stubblefield, Nathan T Uter, David G Myszka, Christopher P Hill & Wesley I Sundquist

]]> Structural basis for ESCRT-III protein autoinhibition Monika Bajorek Heidi L Schubert John McCullough Charles Langelier Debra M Eckert William-May B Stubblefield Nathan T Uter David G Myszka Christopher P Hill Wesley I Sundquist doi:10.1038/nsmb.1621 Nature Structural & Molecular Biology 16, 754 (2009) 2009-06-14 Nature Structural & Molecular Biology 2009-06-14 16 7 Article 754 762 ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing http://dx.doi.org/10.1038/nsmb.1611 Covalent histone modifications can affect the structure of chromatin. Expression of underlying monomethylated histone H3K27 is associated with chromocenters in Arabidopsis, but its presence is unaffected by mutations in the expected methyltransferases. Data now indicate that this modification is catalyzed by Arabidopsis ATRX5 and ATXR6 and is required for silencing, but in a pathway independent of that involving DNA methyltransferases. ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing

Nature Structural & Molecular Biology 16, 763 (2009). doi:10.1038/nsmb.1611

Authors: Yannick Jacob, Suhua Feng, Chantal A LeBlanc, Yana V Bernatavichute, Hume Stroud, Shawn Cokus, Lianna M Johnson, Matteo Pellegrini, Steven E Jacobsen & Scott D Michaels

]]> ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing Yannick Jacob Suhua Feng Chantal A LeBlanc Yana V Bernatavichute Hume Stroud Shawn Cokus Lianna M Johnson Matteo Pellegrini Steven E Jacobsen Scott D Michaels doi:10.1038/nsmb.1611 Nature Structural & Molecular Biology 16, 763 (2009) 2009-06-07 Nature Structural & Molecular Biology 2009-06-07 16 7 Article 763 768 AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity http://dx.doi.org/10.1038/nsmb.1623 AID is a DNA cytidine deaminase that participates in the generation of antibody diversity. AID's mutagenic activity is carefully controlled by transcriptional and post-translational mechanisms. Now the enzyme's intrinsic catalytic activity is found to have been kept low during evolution, and in vitro–selected AID upmutants can cause genetic instability. AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity

Nature Structural & Molecular Biology 16, 769 (2009). doi:10.1038/nsmb.1623

Authors: Meng Wang, Zizhen Yang, Cristina Rada & Michael S Neuberger

]]> AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity Meng Wang Zizhen Yang Cristina Rada Michael S Neuberger doi:10.1038/nsmb.1623 Nature Structural & Molecular Biology 16, 769 (2009) 2009-06-21 Nature Structural & Molecular Biology 2009-06-21 16 7 Article 769 776 H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming http://dx.doi.org/10.1038/nsmb.1629 Covalent histone modifications have been linked to many DNA processes. The repertoire of modifications is still growing, and histone H3K64 trimethylation is now shown to be localized to pericentric chromatin and its levels dynamically altered during developmental reprogramming in both embryos and primordial germ cells. H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming

Nature Structural & Molecular Biology 16, 777 (2009). doi:10.1038/nsmb.1629

Authors: Sylvain Daujat, Thomas Weiss, Fabio Mohn, Ulrike C Lange, Céline Ziegler-Birling, Ulrike Zeissler, Michael Lappe, Dirk Schübeler, Maria-Elena Torres-Padilla & Robert Schneider

]]> H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming Sylvain Daujat Thomas Weiss Fabio Mohn Ulrike C Lange Céline Ziegler-Birling Ulrike Zeissler Michael Lappe Dirk Schübeler Maria-Elena Torres-Padilla Robert Schneider doi:10.1038/nsmb.1629 Nature Structural & Molecular Biology 16, 777 (2009) 2009-06-28 Nature Structural & Molecular Biology 2009-06-28 16 7 Article 777 781 Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex http://dx.doi.org/10.1038/nsmb.1618 The nuclear pore complex mediates nucleocytoplasmic transport and consists of an assembly of multiple copies of ∼30 different proteins called nucleoporins. Kampmann and Blobel describe the structure and flexibility of the heptameric Nup84 complex by single-particle, negative-stain EM. They find that the arrangement of β-propeller and α-solenoid folds within the heptamer resembles that of the clathrin triskelion, which has been proposed to share a common evolutionary origin with the heptameric complex. Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex

Nature Structural & Molecular Biology 16, 782 (2009). doi:10.1038/nsmb.1618

Authors: Martin Kampmann & Günter Blobel

]]> Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex Martin Kampmann Günter Blobel doi:10.1038/nsmb.1618 Nature Structural & Molecular Biology 16, 782 (2009) 2009-06-07 Nature Structural & Molecular Biology 2009-06-07 16 7 Article 782 788 Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F http://dx.doi.org/10.1038/nsmb.1626 Clostridium botulinum neurotoxins (BoNTs) cleave proteins involved in neurotransmitter release, with different serotypes showing distinct cleavage specificity. The structure of BoNT F with peptide inhibitors based on the VAMP substrate give insight into residues crucial for substrate binding and catalysis. Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F

Nature Structural & Molecular Biology 16, 789 (2009). doi:10.1038/nsmb.1626

Authors: Rakhi Agarwal, James J Schmidt, Robert G Stafford & Subramanyam Swaminathan

]]> Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F Rakhi Agarwal James J Schmidt Robert G Stafford Subramanyam Swaminathan doi:10.1038/nsmb.1626 Nature Structural & Molecular Biology 16, 789 (2009) 2009-06-21 Nature Structural & Molecular Biology 2009-06-21 16 7 Article 789 794 Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 Å resolution http://dx.doi.org/10.1038/nsmb0709-795 Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 Å resolution

Nature Structural & Molecular Biology 16, 795 (2009). doi:10.1038/nsmb0709-795

Authors: Michael A Hanson & Raymond C Stevens

]]> Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 Å resolution Michael A Hanson Raymond C Stevens doi:10.1038/nsmb0709-795 Nature Structural & Molecular Biology 16, 795 (2009) Nature Structural & Molecular Biology 16 7 Retraction 795 795