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Current Opinion in Structural Biology

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https://www.readbyqxmd.com/read/28544984/histo-blood-group-antigens-as-mediators-of-infections
#1
REVIEW
Julie E Heggelund, Annabelle Varrot, Anne Imberty, Ute Krengel
The critical first step of a microbial infection is usually the attachment of pathogens to host cell glycans. Targets on host tissues are in particular the histo-blood group antigens (HBGAs), which are present in rich diversity in the mucus layer and on the underlying mucosa. Recent structural and functional studies have revealed significant new insight into the molecular mechanisms, explaining why individuals with certain blood groups are at increased risk of some infections. The most prominent example of blood-group-associated diseases is cholera, caused by infection with Vibrio cholerae...
May 22, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28528306/the-group-ii-intron-maturase-a-reverse-transcriptase-and-splicing-factor-go-hand-in-hand
#2
REVIEW
Chen Zhao, Anna Marie Pyle
The splicing of group II introns in vivo requires the assistance of a multifunctional intron encoded protein (IEP, or maturase). Each IEP is also a reverse-transcriptase enzyme that enables group II introns to behave as mobile genetic elements. During splicing or retro-transposition, each group II intron forms a tight, specific complex with its own encoded IEP, resulting in a highly reactive holoenzyme. This review focuses on the structural basis for IEP function, as revealed by recent crystal structures of an IEP reverse transcriptase domain and cryo-EM structures of an IEP-intron complex...
May 18, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28514705/a-topologically-diverse-family-of-fluoride-channels
#3
REVIEW
Christian B Macdonald, Randy B Stockbridge
Dual-topology proteins are likely evolutionary antecedents to a common motif in membrane protein structures, the inverted repeat. A family of fluoride channels, the Flucs, which protect microorganisms, fungi, and plants against cytoplasmic fluoride accumulation, has representatives of all topologies along this evolutionary trajectory, including dual-topology homodimers, antiparallel heterodimers, and, in eukaryotes, fused two-domain proteins with an inverted repeat motif. Recent high-resolution crystal structures of dual-topology homodimers, coupled with extensive functional information about both the homodimers and two-domain Flucs, provide a case study of the co-evolution of fold and function...
May 14, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28511148/computational-studies-of-membrane-proteins-from-sequence-to-structure-to-simulation
#4
REVIEW
Phillip J Stansfeld
In this review, I discuss the recent advances in computational approaches to studying membrane protein structures, covering the latest methods for predicting a protein structure from its amino acid sequence, through to methods for assessing the structural dynamics and lipid interactions within molecular simulations of complex biological membranes. These approaches have not only benefited from advances in the computational software and architectures, but have also been assisted by a prodigious rise in the number of both the molecular sequences and experimentally determined membrane protein structures...
May 13, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28505542/computational-modeling-of-protein-assemblies
#5
REVIEW
Neelesh Soni, M S Madhusudhan
Computational methods to predict the 3D structures of protein interactions fall into 3 categories-template based modeling, protein-protein docking and hybrid/integrative modeling. The two most important considerations for modeling methods are sampling and scoring conformations. Sampling has benefitted from techniques such as fast Fourier transforms (FFT), spherical harmonics and higher order manifolds. Scoring complexes to determine binding free energy is still a challenging problem. Rapid advances have been made in hybrid modeling where experimental data are amalgamated with computations...
May 12, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28501339/x-ray-free-electron-laser-single-particle-analysis-for-biological-systems
#6
REVIEW
Osamu Miyashita, Yasumasa Joti
The X-ray free electron laser (XFEL) is a new light source that can produce coherent, ultra-brilliant, femtosecond X-ray pulses. This X-ray beam provides new possibilities for studies in structural biology. In this review, we survey the applications of XFEL to biological systems, with an emphasis on studies of noncrystalline samples. Although atomic-level modeling is not yet achievable, this method enables high-throughput, damage-free imaging of biological samples under near-physiological conditions and is being rapidly developed...
May 10, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28482337/recognition-of-microbial-glycans-by-soluble-human-lectins
#7
REVIEW
Darryl A Wesener, Amanda Dugan, Laura L Kiessling
Human innate immune lectins that recognize microbial glycans can conduct microbial surveillance and thereby help prevent infection. Structural analysis of soluble lectins has provided invaluable insight into how these proteins recognize their cognate carbohydrate ligands and how this recognition gives rise to biological function. In this opinion, we cover the structural features of lectins that allow them to mediate microbial recognition, highlighting examples from the collectin, Reg protein, galectin, pentraxin, ficolin and intelectin families...
May 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28482279/improving-certainty-in-single-molecule-imaging
#8
REVIEW
John Sh Danial, Ana J García-Sáez
The spatiotemporal organization of biological entities and the complex network of interactions they sponsor has proven challenging to visualize. Modern biophysics has brought a wealth of techniques for probing cellular structure and dynamics of which fluorescence-based single molecule detection has emerged as a powerful tool. In this review, we summarize notable breakthroughs in biological research based on single molecule imaging, identify prevailing shortcomings in single molecule detection and present current opinion on ameliorating some of its limitations for wider applicability...
May 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28482214/active-state-structures-of-g-protein-coupled-receptors-highlight-the-similarities-and-differences-in-the-g-protein-and-arrestin-coupling-interfaces
#9
REVIEW
Byron Carpenter, Christopher G Tate
G protein-coupled receptors (GPCRs) regulate cellular signalling through heterotrimeric G proteins and arrestins in response to an array of extracellular stimuli. Structure determination of GPCRs in an active conformation bound to intracellular signalling proteins has proved to be highly challenging. Nonetheless, three new structures of GPCRs in an active state have been published during the last year, namely the adenosine A2A receptor (A2AR) bound to an engineered G protein, opsin bound to visual arrestin and the μ opioid receptor (μOR) bound to a G protein-mimicking nanobody...
May 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28460216/protein-structural-motifs-in-prediction-and-design
#10
REVIEW
Craig O Mackenzie, Gevorg Grigoryan
The Protein Data Bank (PDB) has been an integral resource for shaping our fundamental understanding of protein structure and for the advancement of such applications as protein design and structure prediction. Over the years, information from the PDB has been used to generate models ranging from specific structural mechanisms to general statistical potentials. With accumulating structural data, it has become possible to mine for more complete and complex structural observations, deducing more accurate generalizations...
April 28, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28458055/retroviral-intasomes-arising
#11
REVIEW
Alan N Engelman, Peter Cherepanov
Retroviral DNA integration takes place in the context of the intasome nucleoprotein complex. X-ray crystal structures of functional spumaviral intasomes were previously revealed to harbor a homotetramer of integrase, and it was generally believed that integrase tetramers catalyzed the integration of other retroviruses. The elucidation of new structures from four different retroviruses over the past year has however revealed this is not the case. The number of integrase molecules required to construct the conserved intasome core structure differs between viral species...
April 27, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28437704/conserved-rna-polymerase-ii-initiation-complex-structure
#12
REVIEW
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
https://www.readbyqxmd.com/read/28419835/the-architecture-and-function-of-the-chromatin-replication-machinery
#13
REVIEW
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
https://www.readbyqxmd.com/read/28407563/recent-advances-in-fret-for-the-study-of-protein-interactions-and-dynamics
#14
REVIEW
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
https://www.readbyqxmd.com/read/28390861/continually-emerging-mechanistic-complexity-of-the-multi-enzyme-cellulosome-complex
#15
REVIEW
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
https://www.readbyqxmd.com/read/28365498/microbial-glycoproteomics
#16
REVIEW
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 31, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28364585/network-analysis-and-in-silico-prediction-of-protein-protein-interactions-with-applications-in-drug-discovery
#17
REVIEW
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
https://www.readbyqxmd.com/read/28363124/structural-principles-controlling-hiv-envelope-glycosylation
#18
REVIEW
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
https://www.readbyqxmd.com/read/28349863/structural-perspective-of-cooperative-transcription-factor-binding
#19
REVIEW
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
https://www.readbyqxmd.com/read/28343095/ion-mobility-mass-spectrometry-and-orthogonal-gas-phase-techniques-to-study-amyloid-formation-and-inhibition
#20
REVIEW
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
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