July 2009 Volume 16 Number 7, pp 677 - 795
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EDITORIAL
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Welcoming the best and the brightest from everywhere p677
The US State Department promises to accelerate the visa process for
foreign graduate students and postdoctoral researchers. That will be
a welcome change.
doi:10.1038/nsmb0709-677
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COMMENTARY
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WDR5, a complexed protein pp678 - 680
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.
Raymond C Trievel and Ali Shilatifard
doi:10.1038/nsmb0709-678
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----------------------
NEWS AND VIEWS
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Energetics of protein hydrogen bonds pp681 - 682
In this issue, an article gives insight into the microenvironment's
influence on the contribution of hydrogen bonds to protein stability.
C Nick Pace
doi:10.1038/nsmb0709-681
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----------------------
RESEARCH HIGHLIGHTS
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Research highlights p683
doi:10.1038/nsmb0709-683
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ARTICLES
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Localized thermodynamic coupling between hydrogen bonding and
microenvironment polarity substantially stabilizes proteins
pp684 - 690
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.
Jianmin Gao, Daryl A Bosco, Evan T Powers and Jeffery W Kelly
doi:10.1038/nsmb.1610
Abstract: http://links.ealert.nature.com/ctt?kn=112&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=67&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
The structure of SHH in complex with HHIP reveals a recognition role
for the Shh pseudo active site in signaling pp691 - 697
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.
Ivan Bosanac et al.
doi:10.1038/nsmb.1632
Abstract: http://links.ealert.nature.com/ctt?kn=86&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=81&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structural insights into hedgehog ligand sequestration by the human
hedgehog-interacting protein HHIP pp698 - 703
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.
Benjamin Bishop et al.
doi:10.1038/nsmb.1607
Abstract: http://links.ealert.nature.com/ctt?kn=92&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=38&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structural determinants of gating in the TRPV1 channel pp704 - 710
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.
Hector Salazar et al.
doi:10.1038/nsmb.1633
Abstract: http://links.ealert.nature.com/ctt?kn=88&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=44&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
The Hsp82 molecular chaperone promotes a switch between unextendable
and extendable telomere states pp711 - 716
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.
Diane C DeZwaan, Oyetunji A Toogun, Frank J Echtenkamp and Brian C Freeman
doi:10.1038/nsmb.1616
Abstract: http://links.ealert.nature.com/ctt?kn=85&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=105&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Control of alternative splicing through siRNA-mediated
transcriptional gene silencing pp717 - 724
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.
Mariano Allo et al.
doi:10.1038/nsmb.1620
Abstract: http://links.ealert.nature.com/ctt?kn=8&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=25&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structure of a lamprey variable lymphocyte receptor in complex with
a protein antigen pp725 - 730
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.
C Alejandro Velikovsky et al.
doi:10.1038/nsmb.1619
Abstract: http://links.ealert.nature.com/ctt?kn=20&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=66&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structural evidence for consecutive Hel308-like modules in the
spliceosomal ATPase Brr2 pp731 - 739
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.
Lingdi Zhang et al.
doi:10.1038/nsmb.1625
Abstract: http://links.ealert.nature.com/ctt?kn=94&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=43&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structure of a functional ribonucleoprotein pseudouridine synthase
bound to a substrate RNA pp740 - 746
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.
Bo Liang et al.
doi:10.1038/nsmb.1624
Abstract: http://links.ealert.nature.com/ctt?kn=13&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=115&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
A UPF3-mediated regulatory switch that maintains RNA surveillance
pp747 - 753
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.
Wai-Kin Chan et al.
doi:10.1038/nsmb.1612
Abstract: http://links.ealert.nature.com/ctt?kn=1&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=108&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Structural basis for ESCRT-III protein autoinhibition pp754 - 762
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.
Monika Bajorek et al.
doi:10.1038/nsmb.1621
Abstract: http://links.ealert.nature.com/ctt?kn=21&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=31&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
ATXR5 and ATXR6 are H3K27 monomethyltransferases required for
chromatin structure and gene silencing pp763 - 768
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.
Yannick Jacob et al.
doi:10.1038/nsmb.1611
Abstract: http://links.ealert.nature.com/ctt?kn=111&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=28&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
AID upmutants isolated using a high-throughput screen highlight the
immunity/cancer balance limiting DNA deaminase activity pp769 - 776
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.
Meng Wang, Zizhen Yang, Cristina Rada and Michael S Neuberger
doi:10.1038/nsmb.1623
Abstract: http://links.ealert.nature.com/ctt?kn=109&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=51&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
H3K64 trimethylation marks heterochromatin and is dynamically
remodeled during developmental reprogramming pp777 - 781
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.
Sylvain Daujat et al.
doi:10.1038/nsmb.1629
Abstract: http://links.ealert.nature.com/ctt?kn=54&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=118&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Three-dimensional structure and flexibility of a membrane-coating
module of the nuclear pore complex pp782 - 788
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 beta-propeller and alpha-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.
Martin Kampmann and Gunter Blobel
doi:10.1038/nsmb.1618
Abstract: http://links.ealert.nature.com/ctt?kn=17&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=99&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Mode of VAMP substrate recognition and inhibition of Clostridium
botulinum neurotoxin F pp789 - 794
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.
Rakhi Agarwal, James J Schmidt, Robert G Stafford and Subramanyam
Swaminathan
doi:10.1038/nsmb.1626
Abstract: http://links.ealert.nature.com/ctt?kn=11&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=95&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
----------------------
RETRACTION
----------------------
Retraction: Cocrystal structure of synaptobrevin-II bound to
botulinum neurotoxin type B at 2.0 A resolution p795
Michael A Hanson and Raymond C Stevens
doi:10.1038/nsmb0709-795
http://links.ealert.nature.com/ctt?kn=15&m=33525520&r=MTc2OTcxOTY5MQS2&b=2&j=NTI2NTE1MTMS1&mt=1&rt=0
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