Nature Structural & Molecular Biology publishes top-quality research providing insight into how molecular components work together in biological processes.
2024 marks 30 years since we published the first volume of NSMB!
to celebrate, throughout 2024, we will be reflecting on the road covered & looking towards the future -
check out many of the wonderful pieces from our readers, plus some of our thoughts:
Anthony Roberts & co report a
#cryoEM
structure of dynein-2 complex, suggesting mechanisms behind autoinhibition and transport on anterograde IFT trains
With News & Views by Susan Dutcher
Crowdsourcing success
@UWproteindesign
! Foldit players design f 56 new stable proteins from scratch, representing 20 different folds, including one not observed in natural proteins. Four newly determined structures validate the designs.
A
#cryoEM
structure of the active human melatonin receptor
#GPCR
in complex with Gi reveals conformational changes upon activation and basis for G-protein selectivity. Work from the Nureki, Inoue (
@TohokuSeika
) and Nishizawa labs led by
@hhokamoto_en
Wolf
@oistedu
, Aizawa and colleagues use
#cryoEM
to reveal 11 different conformations in the curved flagellar hook See also NV from Ed Egelman , covering this and related work from the Namba group.
🐱🧬AUGUST ISSUE IS OUT! 🧬🐱
X-chromosome inactivation - insights from the active and inactive X chromosome
We featured 3 papers on the cover, which investigate the molecular mechanisms of dosage compensation in mammals.
issue:
Biochemical and cell-based assays reveal that PARP inhibitors impede maturation of nascent DNA strands during replication and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these anti-cancer compounds.
Biochemical and cell-based assays reveal that PARP inhibitors impede maturation of nascent DNA strands during replication and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these anti-cancer compounds.
Nanodiscs rule! Lipid environment promotes GPCR–G protein extensive interactions, as shown for neurotensin receptor by the Wagner, Nasr &
@alanbrownhms
labs
@harvardmed
.
📸another gentle reminder for the ongoing cover competition! 📸
Want to be featured on NSMB cover? submit a spectacular photo, a beautiful piece of data, an insightful drawing to our 30th anniversary cover competition.
Deadline - end of November
#ICYMI
: David Baker & colleagues
@UWproteindesign
describe two de novo designed protein classes that link phosphorylation by tyrosine and serine kinases to protein-protein association and provide potential new avenues to regulate cell function.
Check out our Special Issue on Ubiquitin Biology !
We feature some really exciting science on the mechanisms underlying writing and reading ubiquitylation + some very thoughtful comments and perspectives on the field
Work by
@helin_kristian
& colleagues shows that PRMT5 methylates the splice regulator SRSF1, causing changes in alternative splicing of multiple essential genes required for leukemia cell survival.
Want to be featured on NSMB cover? Submit a spectacular photo, a beautiful piece of data, an insightful drawing to our 30th anniversary cover competition.
Details:
Zhou & colleagues
@NIEHS
show that DNA polymerase δ extrinsically proofreads errors made by both Pol ε and itself, and that the symmetry of
#replication
fidelity is achieved by cooperative efforts of intrinsic & extrinsic proofreading and
#DNA
MMR
Piwi-directed heterochromatin: On the cover of our February issue, we highlight work by
@changwei_yu
@juliusbrennecke
&al
@IMBA_Vienna
on Panoramix SUMOylation on chromatin, connecting the piRNA pathway to heterochromatin formation. Full issue:
HAPPY 30th BIRTHDAY TO US🎂
First issue of NSMB came out in January 1994. Come celebrate with us 30 years of changes and progress in structural and molecular biology
We are continuing celebrations throughout the year with more content, so stay tuned!
Structure maps of RNAs localized to chromatin, nucleoplasm and cytoplasm reveal an intricate interplay of
#RNA
structure, RNA-protein interactions and RNA modifications
Chaperones too can aggregate! Work from
@buchnerlab_tum
on eye lenses from mouse strains with mutations in α-, β-, or γ-crystallins challenge the prevalent model for cataract formation.
#proteostasis
#chaperones
TET2-mediated hm5C modification of tRNA affects the levels of tRNA fragments (tRFs), which have previously been linked to the regulation transposable elements, translation and epigenetic inheritance.
The case for post-predictional modifications in the AlphaFold Protein Structure Database: In this correspondence
@GABRAHREX
@2016Carl
@ElisaTelisa
@glycojones
present an approach to include post-translational modifications in
#AlphaFold
predictions.
Tn7 transposition depends on its AAA+ ATPase adaptor TnsC. A new
#cryoEM
structure from
@alba_guarne
&
@shen_yao10
@mcgillu
shows how TnsC targets DNA sequences between target & insertion sites to regulate sequence-specific transposon insertion.
#CryoEM
structure of the 80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 allows binding at the mRNA exit of the ribosome, ensuring efficient mRNA degradation after the last round of translation.
DOPEGAL, a metabolite of noradrenaline in the locus coeruleus, covalently modifies Tau and accelerates its aggregation and propagation, leading to cognitive deficits in Alzheimer’s disease.
A study by Liz Carpenter and colleagues
@UniofOxford
@thesgconline
reports the first crystal structure of a human ELOVL revealing an unexpected reaction mechanism & suggesting potential approaches for inhibition to treat disease
The expressome, a supercomplex with actively transcribing RNA polymerase and translating ribosome, is seen in Mycoplasma pneumoniae cells, using integrative approach combining cryo-ET and crosslinking/MS analyses. From Mahamid lab
@embl
&
@RappsilberLab
Ingolia lab carried out a systematic survey of the budding yeast proteome and identified hundreds of post-transcriptional regulators. Regulatory activity often lies within intrinsically disordered regions
@nickingolia
@KendraReynaud
Paired-Seq - a new ultra high-throughput method for the parallel analysis of open chromatin and transcriptome in millions of single cells from Bing Ren & colleagues
On the cover of our August 2021 issue, we highlight recent work by Brandão, Ren,
@xindanw
@leonidmirny
and colleagues reporting beautiful Hi-C plots resembling historic tiles. Check out the full issue here:
Check out this collection of articles we helped put together for
@NaturePortfolio
in honor of
@DJuliusSF
and
@ardemp
, recipients of the the Nobel Prize in Physiology or Medicine 2021. Includes some amazing structural biology!
A fresh start: Meissner & colleagues
@MPI_MolGen
provide further evidence that Dnmt1 displays global de novo methylation activity, especially at retrotransposons
Target practice: first Piwi structure with RNA
In this short piece, we highlight recent work by MacRae lab
@scrippsresearch
published in
@Nature
working out how Piwi selectively finds its transposable element RNA targets with the help of piRNA guides.
❄️our January issue is live❄️
on the cover we feature work from
@davidwtaylorjr
&
@ArlenJohnson8
labs on how a single 2′-O-methylation of rRNA gates assembly of a functional ribosome
#CryoEM
reveals structural basis for coupling specificity of one
#GPCR
, the β1-adrenergic receptor, to two different families of G-proteins. Work by Xin-Yung Huang
@WeillCornell
@HiteLabMSKCC
and colleagues.
#cryoEM
structures of human ribosome nascent chain complexes stalled by the drug-like molecule PF846 reveal its mechanism of action and follow up screens show its context dependent function.
Combination of a bicistronic biosensor w/ single-molecule tracking & computational modelling reveals kinetics of cap- vs IRES-mediated translation & shows that IRES bursts are shorter & rarer than bursts of cap translation, which reverses upon stress
🌊SEPTEMBER ISSUE IS ONLINE 🌊
We featured work from
@WilsonLab2
on the cover, where authors present structures of 17 antibiotics bound to E.coli ribosomes.
the full issue:
Our April issue cover features Strychnos toxifera, a plant from which the arrow poison curare can be extracted. Cryo-EM structures of muscle nicotinic receptors by
@RyanHibbs10
@MahfuzRahmanPhD
&al
@UTSWBrain
reveal its mechanism of action. Full issue:
#ICYMI
: Ribosome cryoEM structures by
@FujimoriLabUCSF
@fraser_lab
@shuramankin
&al w/ the antibiotics linezolid & radezolid bound to the peptidyl transferase center & adjacent growing nascent peptide chain provide explanation for context-specific action.
New work from David Ron's lab
@Cambridge_Uni
@TheCIMR
: Structures of the dephosphorylation complex of eIF2α-P reveal how contacts with the regulatory PPP1R15A subunit mediate substrate selectivity.
Live cell imaging of tagged genomic loci reveals clusters of distal enhancers in close proximity to target genes, creating a nano-environment wherein site-specifically recruited enhancer-associated regulatory factors activate transcription.
NSMB celebrates the 50th year of eukaryotic gene transcription with a Focus collection of Reviews and Perspectives by Bob Roeder, Jim Kadonaga, Joan & Ron Conaway and John Lis
NSMB editor Beth Moorefield looks forward to meeting you at
@CSHL
#moet2019
Stretching the resolution limit of atomic force microscopy:
News and Views by
@hoogenboom_lab
highlighting and explaining an improved AFM technique called 'Localization AFM' developed by
@George_R_Heath
@ScheuringLab
recently published in
@Nature
Using
#cryoEM
, Christoph W. Müller & colleagues
@EMBL
@EMBLHeidelberg
structurally investigate elongating RNA polymerase I at 2.7 Å as well as an RNA polymerase I open complex at 3.3 Å and bound to initiation factor RRN3 at 3.2 Å.
Two papers on Chlamydomonas cilia, from Vale lab
@HHMIJanelia
and from
@alanbrownhms
@harvardmed
& Zhang
@wustl
, provide unprecedented detail into the radial spoke architecture and new insights into mechanoregulation.
High-resolution cryo-EM structures of human ATM bound to ATPγS and two distinct ATM inhibitors provide insights into the mechanism of inhibitor selectivity and offer a framework for structure-based drug design.
Here, the authors use cryo-EM to solve the Arabidopsis thaliana Argonaute10 (AtAgo10)-guide RNA complex with and without a target RNA representing a slicing substrate, to provide insights into the slicing mechanism of a eukaryotic AGO
Rowland lab
@NKI_nl
and
@dpanne1
show how SGO1 protects centromeric cohesin from WAPL-mediated release until the kinetochore/microtubules have formed functional attachments. They also show that SGO1 and CTCF similarly bind cohesin.
Kern et al. show how LRRC8A:C volume regulated channels assemble into heteromers and use pore-bound lipids to block conduction in a closed state.
@kerndm
,
@SteveBrohawn
#ionchannels
#cryoem
#cryoEM
structures of human IMPDH1, a metabolic enzyme important in retinal function and disease, reveal polymorphic filaments. Blindness-associated IMPDH1 mutations are characterized & half disrupt feedback inhibition. Work by
@kollmanlab
@aniburr
&al
@UW
Beautiful 'butterfly' structure of RNase PNK reveals two molecular switches that coordinate nuclease and kinase function of this multi-enzyme pre-rRNA processing complex.
The structure of the SALL4-Pomalidomide-Cereblon-DDB1 complex provides insights for rational design of cereblon binding drugs with reduced teratogenic risk.
Dynamic changes in 2’-O-methylation of
#rRNA
in human cells lead to
#ribosome
heterogeneity and result in altered translation of select mRNAs, correlating with changes in cellular phenotypes. Work by
@therealLundLab
@UCPH_BRIC
Acetylation takes aim at mRNA: Choi & Meyer highlight a study by Oberdoerffer, Coller & co published in
@CellCellPress
, which identifies acetylated cytidine as a widespread mark in mRNAs that influences RNA stability and translation
#ICYMI
:
#cryoEM
structures of the metazoan GET complex which targets nascent tail-anchored membrane proteins to the endoplasmic reticulum reveal interactions that coordinate client transfer between two protein chaperones. Work from
@sshaolab
@harvardmed
#ICYMI
: PTEN is a key cell signaling lipid phosphatase that is regulated by C-terminal phosphorylation. Philip A. Cole and colleagues
@harvardmed
@BrighamWomens
@BWHGenetics
now used biophysical methods...(1/2)
Cryo-EM and X-ray crystal structures reveal the architecture of the human Xkr8-Basigin
#scramblase
complex, providing insights into the molecular mechanism of phospholipid scrambling. Work by Shigekazu Nagata and colleagues
@osaka_univ
@osaka_univ_e
From the Urban lab
@JohnsHopkins
@sciencemagazine
: intramembrane rhomboid proteases distort surrounding lipids, allowing much faster diffusion than other integral membrane proteins.
Perspective by Wolfe
#cryoEM
structures of E. coli MutS at sequential stages of the ATP hydrolysis cycle reveal how ATP binding and hydrolysis and its modulation by DNA enable MutS to adopt different conformations during mismatch repair. Work by
@ABorsellini
&al
@LUMC_Leiden
Zagotta & colleagues at
@UWBiochemistry
use tmFRET and Rosetta tools to develop a model for the HCN channel VSD under conditions of membrane hyperpolarization.
.
@RyanHibbs10
@MahfuzR1985
&al
@UTSWBrain
reveal how the electric organ & skeletal muscle nicotinic acetylcholine receptor desensitizes in response to agonist & how the arrow poison curare antagonizes the channel by stabilizing a desensitized state.
News & Views by Dylan Taatjes
@CUBoulder
highlighting and comparing recent
#CryoEM
structures of the human transcription preinitiation complex (PIC) from the
@YuanHe_NWU
@CramerLab
and Yanhui Xu labs.
LOL is for "localization of lipoprotein": Haohao Dong
@SiChuanUniv
and colleagues reveal the structural basis for how the LolCDE system mediates transport of bacterial lipoproteins to the outer membrane
#cryoEM