Read by QxMD icon Read

Current Opinion in Structural Biology

Merle Hantsche, Patrick Cramer
Recent cryo-electron microscopic studies have arrived at atomic models of the core transcription initiation complex comprising RNA polymerase (Pol) II and the basal transcription factors TBP, TFIIA, TFIIB, TFIIE, and TFIIF. A detailed comparison of two independently derived yeast and human core initiation complex structures reveals that they are virtually identical, demonstrating the conservation of the basic transcription machinery amongst eukaryotes. The additional factors TFIID, TFIIH, and Mediator have been located on the periphery of the core initiation complex, providing the topology of the entire initiation assembly, which comprises approximately 70 polypeptides with a molecular weight of ∼4 Megadalton...
April 21, 2017: Current Opinion in Structural Biology
Thomas Cr Miller, Alessandro Costa
Genomic DNA in eukaryotic cells is packaged into nucleosome arrays. During replication, nucleosomes need to be dismantled ahead of the advancing replication fork and reassembled on duplicated DNA. The architecture and function of the core replisome machinery is now beginning to be elucidated, with recent insights shaping our view on DNA replication processes. Simultaneously, breakthroughs in our mechanistic understanding of epigenetic inheritance allow us to build new models of how histone chaperones integrate with the replisome to reshuffle nucleosomes...
April 15, 2017: Current Opinion in Structural Biology
Kenji Okamoto, Yasushi Sako
Förster/fluorescence resonance energy transfer (FRET) has been extensively used to detect the binding state or conformation of biomolecules. In the past few decades, various in vitro and in vivo applications of FRET measurement have been developed, including FRET probes, in-cell measurements, single-molecule measurements, and combination with computer simulation. In this review, we describe recent advances in FRET methods for examining biomolecular interactions and dynamics: (i) phasor plot analysis for quantitative analysis of protein interactions, (ii) single-molecule FRET measurement for detecting conformational dynamics in live cells, and (iii) data assimilation using molecular dynamics simulation to evaluate conformation of the whole protein...
April 10, 2017: Current Opinion in Structural Biology
Steven P Smith, Edward A Bayer, Mirjam Czjzek
The robust plant cell wall polysaccharide-degrading properties of anaerobic bacteria are harnessed within elegant, marcomolecular assemblages called cellulosomes, in which proteins of complementary activities amass on scaffold protein networks. Research efforts have focused and continue to focus on providing detailed mechanistic insights into cellulosomal complex assembly, topology, and function. The accumulated information is expanding our fundamental understanding of the lignocellulosic biomass decomposition process and enhancing the potential of engineered cellulosomal systems for biotechnological purposes...
April 6, 2017: Current Opinion in Structural Biology
Adnan Halim, Jan Haug Anonsen
Mass spectrometry-based "-omics" technologies are important tools for global and detailed mapping of post-translational modifications. Protein glycosylation is an abundant and important post translational modification widespread throughout all domains of life. Characterization of glycoproteins, including identification of glycan structure and components, their attachment sites and protein carriers, remains challenging. However, recent advances in glycoproteomics, a subbranch that studies and categorizes protein glycosylations, have greatly expanded the known protein glycosylation space and research in this area is rapidly accelerating...
March 30, 2017: Current Opinion in Structural Biology
Yoichi Murakami, Lokesh P Tripathi, Philip Prathipati, Kenji Mizuguchi
Protein-protein interactions (PPIs) are vital to maintaining cellular homeostasis. Several PPI dysregulations have been implicated in the etiology of various diseases and hence PPIs have emerged as promising targets for drug discovery. Surface residues and hotspot residues at the interface of PPIs form the core regions, which play a key role in modulating cellular processes such as signal transduction and are used as starting points for drug design. In this review, we briefly discuss how PPI networks (PPINs) inferred from experimentally characterized PPI data have been utilized for knowledge discovery and how in silico approaches to PPI characterization can contribute to PPIN-based biological research...
March 29, 2017: Current Opinion in Structural Biology
Vincenzo Carnevale, Michael L Klein
Voltage gated sodium channels are fundamental players in animals physiology. By triggering the depolarization of the lipid membrane they enable generation and propagation of the action potential. The involvement of these channels in numerous pathological conditions makes them relevant target for pharmaceutical intervention. Therefore, modulation of sodium conductance via small molecule binding constitutes a promising strategy to treat a large variety of diseases. However, this approach entails significant challenges: voltage gated sodium channels are complex nanomachines and the details of their workings have only recently started to become clear...
March 28, 2017: Current Opinion in Structural Biology
Anna-Janina Behrens, Max Crispin
The heavily glycosylated, trimeric HIV-1 envelope (Env) protein is the sole viral protein exposed on the HIV-1 virion surface and is thus a main focus of antibody-mediated vaccine development. Dense glycosylation at the outer domain of Env constrains normal enzymatic processing, stalling the glycans at immature oligomannose-type structures. Furthermore, native trimerization imposes additional steric constraints, which generate an extensive 'trimer-induced mannose patch'. Importantly, the immature glycans present a highly conserved feature of the virus that is targeted by broadly neutralizing antibodies...
March 28, 2017: Current Opinion in Structural Biology
Jonathan Gardiner Heddle, Soumyananda Chakraborti, Kenji Iwasaki
Advanced electron microscopy techniques have been used to solve many viral capsid structures. The resulting detailed structural knowledge contributes to understanding of the mechanisms of self-assembly, maturation pathways and virion-host cell interactions. It also acts as inspiration for design and production of capsid-like artificial protein cages. Both natural and artificial cages have potential uses in medicine including as vaccines and in drug delivery. For vaccines, virus-like particles formed only from outer virion shells, lacking genetic material, offer the simplest basis for development, while encapsulation of target molecules inside protein cages is potentially more challenging...
March 27, 2017: Current Opinion in Structural Biology
Ekaterina Morgunova, Jussi Taipale
In prokaryotes, individual transcription factors (TFs) can recognize long DNA motifs that are alone sufficient to define the genes that they induce or repress. In contrast, in higher organisms that have larger genomes, TFs recognize sequences that are too short to define unique genomic positions. In addition, development of multicellular organisms requires molecular systems that are capable of executing combinatorial logical operations. Co-operative recognition of DNA by multiple TFs allows both definition of unique genomic positions in large genomes, and complex information processing at the level of individual regulatory elements...
March 24, 2017: Current Opinion in Structural Biology
Waldemar Hoffmann, Gert von Helden, Kevin Pagel
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway...
March 23, 2017: Current Opinion in Structural Biology
Dominika Elmlund, Sarah N Le, Hans Elmlund
Cryogenic electron microscopy (cryo-EM) and single-particle analysis now enables the determination of high-resolution structures of macromolecular assemblies that have resisted X-ray crystallography and other approaches. Successful high-resolution structure determination by cryo-EM always depends on the quality of the protein sample. While structural heterogeneity remains a key challenge for cryo-EM, it also represents a rare opportunity to study the intrinsic conformational flexibility of macromolecular assemblies...
March 22, 2017: Current Opinion in Structural Biology
Frank Noé, Cecilia Clementi
Collective variables are an important concept to study high-dimensional dynamical systems, such as molecular dynamics of macromolecules, liquids, or polymers, in particular to define relevant metastable states and state-transition or phase-transition. Over the past decade, a rigorous mathematical theory has been formulated to define optimal collective variables to characterize slow dynamical processes. Here we review recent developments, including a variational principle to find optimal approximations to slow collective variables from simulation data, and algorithms such as the time-lagged independent component analysis...
March 16, 2017: Current Opinion in Structural Biology
Rachelle Mariano, Stefan Wuchty
The discovery, validation, and characterization of protein-based interactions from different species are crucial for translational research regarding a variety of pathogens, ranging from the malaria parasite Plasmodium falciparum to HIV-1. Here, we review recent advances in the prediction of host-pathogen protein interfaces using structural information. In particular, we observe that current methods chiefly perform machine learning on sequence and domain information to produce large sets of candidate interactions that are further assessed and pruned to generate final, highly probable sets...
March 16, 2017: Current Opinion in Structural Biology
Julia M Shifman, Niv Papo
No abstract text is available yet for this article.
March 14, 2017: Current Opinion in Structural Biology
Sven A Sewitz, Zahra Fahmi, Karen Lipkow
The linear molecules of DNA that constitute a eukaryotic genome have to be carefully organised within the nucleus to be able to correctly direct gene expression. Microscopy and chromosome capture methods have revealed a hierarchical organisation into territories, domains and subdomains that ensure the accessibility of expressed genes and eventually chromatin loops that serve to bring gene enhancers into proximity of their target promoters. A rapidly growing number of genome-wide datasets and their analyses have given detailed information into the conformation of the entire genome, allowing evolutionary insights, observations of genome rearrangements during development and the identification of new gene-to-disease associations...
March 8, 2017: Current Opinion in Structural Biology
Fabio Parmeggiani, Po-Ssu Huang
Repeat proteins present unique opportunities for engineering because of their modular nature that potentially allows LEGO(®) like construction of macromolecules. Nature takes advantage of these properties and uses this type of scaffold for recognition, structure, and even signaling purposes. In recent years, new protein modeling tools facilitated the design of novel repeat proteins, creating possibilities beyond naturally occurring scaffolds alone. We highlight here the different design strategies and summarize the various structural families and novel proteins achieved...
March 3, 2017: Current Opinion in Structural Biology
Sarah L Shammas
Understanding the interactions of proteins involved in transcriptional regulation is critical to describing biological systems because they control the expression profile of the cell. Yet sadly they belong to a less well biophysically characterized subset of proteins; they frequently contain long disordered regions that are highly dynamic. A key question therefore is, why? What functional roles does protein disorder play in transcriptional regulation? Experimental data exemplifying these roles are starting to emerge, with common themes being enabling complexity within networks and quick responses...
March 2, 2017: Current Opinion in Structural Biology
Robert B Best
Intrinsically disordered proteins (IDPs) are increasingly realized to play diverse biological roles, ranging from molecular signaling to the formation of membraneless organelles. Their high degree of disorder makes them more challenging to study using the techniques of conventional structural biology, because any observable will be averaged over a heterogeneous ensemble of structures. Molecular simulations and theory are therefore a natural complement to experiment for studying the structure, dynamics and function of IDPs...
March 1, 2017: Current Opinion in Structural Biology
Bärbel S Blaum
Complement, a part of the humoral innate immune system, is divided into three pathways. The classical and mannose-binding lectin pathways are triggered by specific recognition of foreign targets. Conversely, the alternative pathway (AP) is actively down-regulated on host tissue. Glycosaminoglycans (GAGs) and sialylated glycans mediate host recognition of the AP as self-associated molecular patterns (SAMPs) to the regulatory protein factor H (FH). This review summarizes the more recent years of research on SAMP recognition by FH from a structural biology point of view and discusses implications for two complement-associated conditions, age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS)...
February 9, 2017: Current Opinion in Structural Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"