Advance online publication
The latest research papers, published online ahead of print. These online versions are definitive and may be cited using the digital object identifier (DOI).
About advance online publicationArticles
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
Published online: 28 June 2009 | doi: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.
Abstract - Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP | Full Text - Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP | PDF (821 KB) - Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP | Supplementary information
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
Published online: 28 June 2009 | doi: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.
Abstract - The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling | Full Text - The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling | PDF (708 KB) - The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling | Supplementary information
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
Published online: 28 June 2009 | doi: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.
Abstract - H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming | Full Text - H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming | PDF (615 KB) - H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming | Supplementary information
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
Published online: 28 June 2009 | doi: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.
Abstract - Structural determinants of gating in the TRPV1 channel | Full Text - Structural determinants of gating in the TRPV1 channel | PDF (673 KB) - Structural determinants of gating in the TRPV1 channel | Supplementary information
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F
Rakhi Agarwal, James J Schmidt, Robert G Stafford & Subramanyam Swaminathan
Published online: 21 June 2009 | doi: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.
Abstract - Mode of VAMP substrate recognition and inhibition of : Clostridium botulinum: neurotoxin F | Full Text - Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F | PDF (620 KB) - Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F | Supplementary information
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
Published online: 21 June 2009 | doi: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.
Abstract - Control of alternative splicing through siRNA-mediated transcriptional gene silencing | Full Text - Control of alternative splicing through siRNA-mediated transcriptional gene silencing | PDF (542 KB) - Control of alternative splicing through siRNA-mediated transcriptional gene silencing | Supplementary information
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
Published online: 21 June 2009 | doi: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.
Abstract - Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen | Full Text - Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen | PDF (720 KB) - Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen | Supplementary information
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
Published online: 21 June 2009 | doi: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.
Abstract - AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity | Full Text - AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity | PDF (543 KB) - AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity | Supplementary information
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
Published online: 14 June 2009 | doi: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.
Abstract - Structural basis for ESCRT-III protein autoinhibition | Full Text - Structural basis for ESCRT-III protein autoinhibition | PDF (1,024 KB) - Structural basis for ESCRT-III protein autoinhibition | Supplementary information
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
Published online: 14 June 2009 | doi: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.
Abstract - The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states | Full Text - The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states | PDF (432 KB) - The Hsp82 molecular chaperone promotes a switch between unextendable and extendable telomere states | Supplementary information
Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins
Jianmin Gao, Daryl A Bosco, Evan T Powers & Jeffery W Kelly
Published online: 14 June 2009 | doi: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.
Abstract - Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins | Full Text - Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins | PDF (581 KB) - Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins | Supplementary information
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
Published online: 14 June 2009 | doi:10.1038/nsmb.1625
PDB code
3D view
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.
Abstract - Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2 | Full Text - Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2 | PDF (687 KB) - Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2 | Supplementary information
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
Published online: 07 June 2009 | doi: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.
Abstract - A UPF3-mediated regulatory switch that maintains RNA surveillance | Full Text - A UPF3-mediated regulatory switch that maintains RNA surveillance | PDF (505 KB) - A UPF3-mediated regulatory switch that maintains RNA surveillance | Supplementary information
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
Published online: 07 June 2009 | doi: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.
Abstract - ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing | Full Text - ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing | PDF (553 KB) - ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing | Supplementary information
Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex
Martin Kampmann & Günter Blobel
Published online: 07 June 2009 | doi: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 
-propeller and 
-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.
Abstract - Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex | Full Text - Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex | PDF (872 KB) - Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex | Supplementary information
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
Published online: 28 May 2009 | doi: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.
Abstract - Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA | Full Text - Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA | PDF (1,025 KB) - Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA | Supplementary information
Until print versions of AOP papers are published, they should be cited in the style "Author(s) Nature Structural & Molecular Biology advance online publication, day month year (doi:10.1038/nsmbXXXXX)". Once the print version (identical to the AOP) is published, it should be cited as follows: "Author(s) Nature Structural & Molecular Biology volume, page (year); advance online publication, (doi:10.1038/nsmbXXXXX)".
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