Featured
-
-
Article
| Open AccessIntramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs
The specific recognition of a proline-rich motif in the intrinsically disordered region of SF1 by the PRPF40A tandem WW domains is modulated by an intramolecular autoinhibition, suggesting a general mechanism to enhance WW binding selectivity.
- Santiago Martínez-Lumbreras
- , Lena K. Träger
- & Michael Sattler
-
Article
| Open AccessA hemoprotein with a zinc-mirror heme site ties heme availability to carbon metabolism in cyanobacteria
Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.
- Nicolas Grosjean
- , Estella F. Yee
- & Crysten E. Blaby-Haas
-
Article
| Open AccessMyosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads
Myosin-binding protein C (MyBP-C) resides and interacts with the myosin filaments in striated muscle and regulates contraction via an unclear mechanism. Here, the authors demonstrate that MyBP-C regulates the performance of myosin heads.
- Anthony L. Hessel
- , Nichlas M. Engels
- & Samantha P. Harris
-
Article
| Open AccessComplexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles
X-ray scattering and electron microscopy are used in concert to show that complexes of tubulin oligomers and tau are building blocks of an intervening network that cross-bridge microtubules into bundles with the same linear geometry observed in neurons.
- Phillip A. Kohl
- , Chaeyeon Song
- & Cyrus R. Safinya
-
Article
| Open AccessDisordered regions in proteusin peptides guide post-translational modification by a flavin-dependent RiPP brominase
Here the authors use NMR, SAXS and MD simulations to characterise the structure of proteusin peptides, which are atypically long RiPP substrates. They show a small, unstructured region in the proteusin leader is sufficient for its interaction with a halogenase that brominates the terminal tryptophan residue.
- Nguyet A. Nguyen
- , F. N. U. Vidya
- & Vinayak Agarwal
-
Article
| Open AccessThe acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12
Here, the authors utilise an integrative approach to characterise the fuzzy heterocomplex between CXCL12 and the fully reduced alarmin HMGB1, highlighting the importance of HMGB1’s acidic IDR to the interaction and with cell surface CXCR4.
- Malisa Vittoria Mantonico
- , Federica De Leo
- & Giovanna Musco
-
Article
| Open AccessUnconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56
Structural and functional characterization of an NF-κB-targeting bacterial toxin reveals an unconventional structure and mechanisms of membrane interaction and translocation.
- Johnny Lisboa
- , Cassilda Pereira
- & Nuno M. S. dos Santos
-
Article
| Open AccessStructural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
T-box riboswitches are RNA-based gene regulators, composed of highly structured noncoding RNAs: the T-box and a tRNA ligand. Here, the authors assess the folding of a translational T-box aptamer and dissect the role of Mg2+, intra- and intermolecular RNA-RNA interactions in modulating its folding and function.
- Xiaolin Niu
- , Zhonghe Xu
- & Xianyang Fang
-
Article
| Open AccessDirect observation of tRNA-chaperoned folding of a dynamic mRNA ensemble
T-box riboswitch RNAs directly bind to specific tRNA and regulate the transcription or translation of downstream genes in bacteria. Using single-molecule FRET and ensemble biophysical analyses, here the authors uncover a Venus flytrap-like mechanism where tRNA binding to a T-box riboswitch mRNA triggers its rapid domain closure.
- Krishna C. Suddala
- , Janghyun Yoo
- & Jinwei Zhang
-
Article
| Open AccessStructural basis for specific RNA recognition by the alternative splicing factor RBM5
The RNA binding protein RBM5 regulates alternative splicing of genes implicated in cancer. Here the authors show structural mechanisms how multiple RNA binding domains of RBM5 cooperate to recognize specific target RNA sequences.
- Komal Soni
- , Pravin Kumar Ankush Jagtap
- & Michael Sattler
-
Article
| Open AccessStructures of honeybee-infecting Lake Sinai virus reveal domain functions and capsid assembly with dynamic motions
Viruses can cause Colony Collapse Disorder, leading to large losses of honeybee hives globally. In this study, the authors solve capsid structures of honeybee-infecting Lake Sinai viruses and identify distinct features, which advances understanding of viral dynamics, assembly and infection mechanisms.
- Nai-Chi Chen
- , Chun-Hsiung Wang
- & Chun-Jung Chen
-
Article
| Open AccessMolecular architecture of the glycogen- committed PP1/PTG holoenzyme
Glycogen metabolism is tightly regulated. Here the authors describe the 3D structure of the PP1/PTG protein complex, which plays a prominent role in the activation of glycogen synthesis and in the pathogenesis of Lafora disease, the most severe form of pediatric progressive epilepsy.
- Marta Stefania Semrau
- , Gabriele Giachin
- & Graziano Lolli
-
Article
| Open AccessStructural basis for the mechanisms of human presequence protease conformational switch and substrate recognition
Presequence protease (PreP) is essential to mitochondrial proteostasis. This study leverages advanced vitrification techniques to solve cryoEM structures of apo- and substrate-bound PreP and integrates these data with other analysis to reveal key stages and mechanistic insights of the PreP catalytic cycle.
- Wenguang G. Liang
- , Juwina Wijaya
- & Wei-Jen Tang
-
Article
| Open AccessStructure of Vibrio collagenase VhaC provides insight into the mechanism of bacterial collagenolysis
The collagenolytic mechanism of Vibrio collagenase, a virulence factor, remains unclear. Here, the authors report the structure of Vibrio collagenase VhaC and propose the mechanism for collagen recognition and degradation, providing new insight into bacterial collagenolysis.
- Yan Wang
- , Peng Wang
- & Yu-Zhong Zhang
-
Article
| Open AccessMechanism of phosphate sensing and signaling revealed by rice SPX1-PHR2 complex structure
SPX proteins sense phosphate levels in plant cells by binding to inositol polyphosphates (InsP) and suppressing the activity of PHR transcription factors. Here the authors show that when bound to InsP6, the rice SPX1 protein inhibits the activity of PHR2 by attenuating both its dimerization and DNA binding activity.
- Jia Zhou
- , Qinli Hu
- & Weiman Xing
-
Article
| Open AccessRegulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker
Eph receptor tyrosine kinases and their ephrin ligands mediate cell-cell communication. Here, the authors assess the structure and dynamics of the EphA2 intracellular region and uncover complex effects of phosphorylation within the linker region between EphA2 kinase and SAM domains.
- Bernhard C. Lechtenberg
- , Marina P. Gehring
- & Elena B. Pasquale
-
Article
| Open AccessPseudoknot length modulates the folding, conformational dynamics, and robustness of Xrn1 resistance of flaviviral xrRNAs
Exoribonuclease-resistant RNAs (xrRNAs) are RNA elements that block the exoribonucleolytic degradation of RNA. Here the authors show how a long-range pseudoknot length modulates the Mg2+-dependence of flaviviral xrRNA’s folding, conformational dynamics and Xrn1 resistance.
- Xiaolin Niu
- , Ruirui Sun
- & Xianyang Fang
-
Article
| Open AccessConformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism
The endoplasmic-reticulum aminopeptidase ERAP1 processes peptides for antigen presentation. Here, the authors assess ERAP1 conformational states in solution, providing insight into the molecular mechanisms of ERAP1 substrate-length dependent catalytic activity and regulation, including the effects of autoimmune disease-associated polymorphism.
- Zachary Maben
- , Richa Arya
- & Lawrence J. Stern
-
Article
| Open AccessA multi-step nucleation process determines the kinetics of prion-like domain phase separation
The nucleation mechanisms of biological protein phase separation are poorly understood. Here, the authors perform time-resolved SAXS experiments with the low-complexity domain (LCD) of hnRNPA1 and uncover multiple kinetic regimes on the micro- to millisecond timescale. Initially, individual proteins collapse. Nucleation then occurs via two steps distinguished by their protein cluster size distributions.
- Erik W. Martin
- , Tyler S. Harmon
- & Tanja Mittag
-
Article
| Open AccessDesigned and biologically active protein lattices
Organising proteins in 2D and 3D is needed to develop complex bimolecular materials for a range of applications. Here, the authors report the encapsulation of ferritin and apoferritin in DNA-based voxels with programmed assembly to generate both 2D and 3D protein lattices and demonstrate the retention of protein function.
- Shih-Ting Wang
- , Brian Minevich
- & Oleg Gang
-
Article
| Open AccessUltrafast coherent motion and helix rearrangement of homodimeric hemoglobin visualized with femtosecond X-ray solution scattering
Femtosecond time-resolved X-ray solution scattering (fs-TRXSS) measurements provide information on the structural dynamics of proteins in solution. Here, the authors present a structure refinement method for the analysis of fs-TRXSS data and use it to characterise the ultrafast structural changes of homodimeric haemoglobin.
- Yunbeom Lee
- , Jong Goo Kim
- & Hyotcherl Ihee
-
Article
| Open AccessNanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.
- Marios Georgiadis
- , Aileen Schroeter
- & Markus Rudin
-
Article
| Open AccessStructure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis
During clathrin-mediated endocytosis in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for membrane invagination. Here authors present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP2 that constitutes the anchor to the plasma membrane.
- Javier Lizarrondo
- , David P. Klebl
- & Maria M. Garcia-Alai
-
Article
| Open AccessSelf-assembly and regulation of protein cages from pre-organised coiled-coil modules
Coiled-coil protein origami is a strategy for the de novo design of polypeptide nanostructures based on coiled-coil dimer forming peptides, where a single chain protein folds into a polyhedral cage. Here, the authors design a single-chain triangular bipyramid and also demonstrate that the bipyramid can be self-assembled as a heterodimeric complex, comprising pre-defined subunits.
- Fabio Lapenta
- , Jana Aupič
- & Roman Jerala
-
Article
| Open AccessDesigned folding pathway of modular coiled-coil-based proteins
Coiled-coil protein origami (CCPO) is a strategy for the design of polyhedral cage-shaped protein folds based on coiled-coil (CC) dimer-forming peptides. Here, the authors show that CCPO proteins fold in a multistep process governed by the spatial distance between CC modules in the primary sequence and subsequent folding intermediates, which enables the use of identical CC modules for the CCPO tetrahedron design.
- Jana Aupič
- , Žiga Strmšek
- & Roman Jerala
-
Article
| Open AccessStructure of human RNA polymerase III
The eukaryotic RNA Polymerase III transcribes tRNAs, some ribosomal and spliceosomal RNAs. Here, the authors resolve a cryo-EM structure of human RNA Polymerase III in its apo form and complemented it with crystal structures and SAXS analysis of RPC5, revealing insights into the molecular mechanisms of Pol III transcription.
- Ewan Phillip Ramsay
- , Guillermo Abascal-Palacios
- & Alessandro Vannini
-
Article
| Open AccessNucleoid remodeling during environmental adaptation is regulated by HU-dependent DNA bundling
HU is among the most conserved and abundant nucleoid-associated proteins in eubacteria. Here the authors investigate the role of histone-like proteins (HU) in the 3D organization of the bacteria DNA and show via soft X-ray tomography the process of nucleoid remodeling.
- Soumya G. Remesh
- , Subhash C. Verma
- & Michal Hammel
-
Article
| Open AccessAllosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain
Trypanosoma brucei guanosine 5′-monophosphate reductase (TbGMPR) catalyses the conversion of GMP to inosine 5′-monophosphate and contains a cystathionine-β-synthase (CBS) domain. Here the authors combine X-ray crystallography and kinetic measurements and present the GMP-, GTP-bound and nucleotide-free TbGMPR structures and show that guanine and adenine nucleotides are allosteric regulators of TbGMPR that bind to the CBS domain.
- Akira Imamura
- , Tetsuya Okada
- & Takashi Inui
-
Article
| Open AccessConformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90
The chaperone Hsp90 uses the free energy from ATP hydrolysis to control the folding of client proteins in eukaryotic cells. Here the authors provide mechanistic insights into how its catalytic activity is coupled to conformational changes by combining large-scale molecular simulations with NMR, FRET and SAXS experiments.
- Sophie L. Mader
- , Abraham Lopez
- & Ville R. I. Kaila
-
Article
| Open AccessTwo distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation
Ubiquitylation of histone H3 (H3Ub2) by UHRF1 recruits DNMT1 to chromatin, which is essential for DNA methylation inheritance. Here, the authors provide evidence that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are required for high fidelity DNA methylation inheritance.
- Atsuya Nishiyama
- , Christopher B. Mulholland
- & Makoto Nakanishi
-
Article
| Open AccessStructure and mechanism of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate
Antiviral defence type III CRISPR systems produce cyclic oligoadenylates (cOA) as second messengers that activate downstream effectors. Here the authors present the crystal structure of the type III CRISPR defence DNA nuclease Can1 in complex with cyclic tetra-adenylate (cA4) and show that Can1 nicks supercoiled DNA.
- Stephen A. McMahon
- , Wenlong Zhu
- & Tracey M. Gloster
-
Article
| Open AccessCrystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy
Fukutin-related protein (FKRP) catalyses the addition of ribitol-phosphate (RboP) to the O-mannosyl glycan of α-dystroglycan and mutations in FKRP cause dystroglycanopathy. Here the authors provide insights into its oligomerization and recognition of the substrates, CDP-Rbo and the RboP-(phospho-)core M3 glycan, by determining the crystal structures of human FKRP.
- Naoyuki Kuwabara
- , Rieko Imae
- & Ryuichi Kato
-
Article
| Open AccessAcetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
Isocitrate lyase (ICL) isoforms 1 and 2 are enzymes in the glyoxylate and methylcitrate cycles that enable Mycobacterium tuberculosis (Mtb) to use lipids as a carbon source. Here the authors present the ligand-free Mtb ICL2 and acetyl-CoA bound ICL2 crystal structures, which reveal a structural reorganisation upon acetyl-CoA binding that leads to an activation of its isocitrate lyase and methylcitrate lyase activities.
- Ram Prasad Bhusal
- , Wanting Jiao
- & Ivanhoe K. H. Leung
-
Article
| Open AccessThe mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X
DEAD-box helicases (DDXs) function in an ATP-dependent, non-processive manner and the conserved helicase core is composed of two RecA-like domains D1 and D2. Here the authors present the crystal structure of the D1D2 core from human DDX3X bound to a 23-base pair dsRNA in the pre-unwound state and discuss the implications for helicase mechanism.
- He Song
- & Xinhua Ji
-
Article
| Open AccessConvergent allostery in ribonucleotide reductase
Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides, which is an essential step in DNA synthesis. Here the authors use small-angle X-ray scattering, X-ray crystallography, and cryo-electron microscopy to capture active and inactive forms of the Bacillus subtilis RNR and provide mechanistic insights into a convergent form of allosteric regulation.
- William C. Thomas
- , F. Phil Brooks III
- & Nozomi Ando
-
Article
| Open AccessCoherent diffractive imaging of microtubules using an X-ray laser
XFEL radiation is providing new opportunities for probing biological systems. Here the authors perform nanoscale x-ray imaging of microtubules with helical symmetry, by using imaging sorting and reconstruction techniques.
- Gisela Brändén
- , Greger Hammarin
- & Richard Neutze
-
Article
| Open AccessStructure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism
The iron-sulfur cluster (ISC) assembly complex is activated by frataxin (FXN) and Friedreich’s ataxia is caused by FXN deficiency. Here the authors present the 3.2 Å resolution cryo-EM structure of the human frataxin bound ISC complex and discuss how FXN activates enzymatic activity.
- Nicholas G. Fox
- , Xiaodi Yu
- & Seungil Han
-
Article
| Open AccessA study of the extraordinarily strong and tough silk produced by bagworms
Spider silk is widely studied for its structural properties; however, other creatures produce silk that could be of interest. Here, the authors study the properties and structure of Bagworm silk and report it as being extraordinarily strong and tough compared to other known silks.
- Taiyo Yoshioka
- , Takuya Tsubota
- & Tsunenori Kameda
-
Article
| Open AccessHelical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9
Amphihelical antimicrobial peptides (AMPs) are bactericidal host defense factors, but their function as immunomodulators is emerging. Here the authors show that several AMPs organize DNA into periodic nanocrystals by self-assembling into superhelical protofibril scaffolds, which potentiates DNA sensing by TLR9.
- Ernest Y. Lee
- , Changsheng Zhang
- & Gerard C. L. Wong
-
Article
| Open AccessA five-residue motif for the design of domain swapping in proteins
Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.
- Neha Nandwani
- , Parag Surana
- & Shachi Gosavi
-
Article
| Open AccessOCP–FRP protein complex topologies suggest a mechanism for controlling high light tolerance in cyanobacteria
Cyanobacterial photoprotection is controlled by OCP and FRP proteins, but their dynamic interplay is not fully understood. Here, the authors combine protein engineering, disulfide trapping and structural analyses to provide mechanistic insights into the transient OCP-FRP interaction.
- Nikolai N. Sluchanko
- , Yury B. Slonimskiy
- & Eugene G. Maksimov
-
Article
| Open AccessCorrelative microscopy approach for biology using X-ray holography, X-ray scanning diffraction and STED microscopy
X-ray techniques benefit from correlative imaging approaches, but combination with super-resolution microscopy has not been explored. Here the authors image the cardiomyocyte cytoskeleton by combining holographic X-ray imaging, X-ray scanning diffraction and STED in the same synchrotron endstation.
- M. Bernhardt
- , J.-D. Nicolas
- & T. Salditt
-
Article
| Open AccessMultidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
The human estrogen receptor alpha (hERα) is a hormone-responsive transcription factor. Here the authors combine small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling and show that multidomain hERα adopts an L-shaped boot-like architecture revealing a cross-talk between its DNA-binding domain and Ligand-binding domain.
- Wei Huang
- , Yi Peng
- & Sichun Yang
-
Article
| Open AccessStructural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1
hnRNP A1 is an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a, of the oncomiR-1 cluster. Here the authors employ an integrative structural biology approach and provide insights into the molecular mechanism of how hnRNP A1 facilitates pri-mir-18a biogenesis.
- Hamed Kooshapur
- , Nila Roy Choudhury
- & Michael Sattler
-
Article
| Open AccessConformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis
RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.
- Emma J. Petrie
- , Jarrod J. Sandow
- & James M. Murphy
-
Article
| Open AccessStructural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition
The human enzyme MTHFR links the folate and methionine cycles, which are essential for the biosynthesis of nucleotides and proteins. Here, the authors present the crystal structure and biochemical analysis of human MTHFR, providing molecular insights into its function and regulation in higher eukaryotes.
- D. Sean Froese
- , Jolanta Kopec
- & Wyatt W. Yue
-
Article
| Open AccessSelf-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation
The nucleolus is a membrane-less organelle formed through liquid–liquid phase separation (LLPS). Here the authors use biophysical methods and show that the nucleolar protein nucleophosmin (NPM1) also undergoes LLPS through homotypic, inter-NPM1 interactions and discuss implications for the ribosome biogenesis process.
- Diana M. Mitrea
- , Jaclyn A. Cika
- & Richard W. Kriwacki
-
Article
| Open AccessEpsin and Sla2 form assemblies through phospholipid interfaces
Adapter proteins assist clathrin coated pit assembly. Here, the authors combine native mass spectrometry, crystallography and SAXS measurements and show that the membrane–proximal domains of the adaptor proteins epsin and Sla2 form complexes mediated through phosphatidylinositol 4,5-bisphosphate interfaces leading to assembly formation.
- Maria M. Garcia-Alai
- , Johannes Heidemann
- & Rob Meijers
-
Article
| Open AccessStructural analysis of mtEXO mitochondrial RNA degradosome reveals tight coupling of nuclease and helicase components
The mitochondrial RNA degradosome (mtEXO) plays an essential role in the regulation of mitochondrial gene expression and is composed of the 3′-to-5′ exoribonuclease Dss1 and the helicase Suv3. Here the authors present the RNA bound mtEXO crystal structure and give insights into its mechanism.
- Michal Razew
- , Zbigniew Warkocki
- & Marcin Nowotny