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Structural biology
About: Structural biology is a research topic. Over the lifetime, 2206 publications have been published within this topic receiving 126070 citations.
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TL;DR: This article reviews the applications of ncAA incorporation into proteins for determining structural information through various techniques with the main focus on crosslinking mass spectrometry and single-molecule FRET-based techniques.
27 citations
TL;DR: Details of multilayered C2-mediated effects important for SHIP2 activity are revealed and points towards interesting new possibilities for therapeutic interventions.
Abstract: SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain. Both the phosphatase and C2 domains bind phosphatidylserine lipids, which likely helps to position the active site towards its substrate. Although located distant to the active site, the C2 domain greatly enhances catalytic turnover. Employing molecular dynamics, mutagenesis and cell biology, we identify two distinct allosteric signaling pathways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid chain or headgroup moieties of PI(3,4,5)P3. Together, this study reveals details of multilayered C2-mediated effects important for SHIP2 activity and points towards interesting new possibilities for therapeutic interventions.
27 citations
TL;DR: A solid-state NMR technique is proposed that allows for the determination of side-chain dynamics from membrane proteins in lipid bilayers and allows for a wide range of dipolar couplings to be encoded, providing high resolution and sensitivity for systems that undergo motional averaging such as that of amino acid side chains.
Abstract: Despite recent advances in NMR approaches for structural biology, determination of membrane protein dynamics in its native environment continues to be a monumental challenge, as most NMR structural studies of membrane proteins are commonly carried out either in micelles or in vesicle systems under frozen conditions. To overcome this difficulty, we propose a solid-state NMR technique that allows for the determination of side-chain dynamics from membrane proteins in lipid bilayers. This new technique, namely dipolar enhanced polarization transfer (DREPT), allows for a wide range of dipolar couplings to be encoded, providing high resolution and sensitivity for systems that undergo motional averaging such as that of amino acid side chains. NMR observables such as dipolar couplings and chemical shift anisotropy, which are highly sensitive to molecular motions, provide a direct way of probing protein dynamics over a wide range of time scales. Therefore, using an appropriate model, it is possible to determine side-chain dynamics and provide additional information on the topology and function of a membrane protein in its native environment.
27 citations
27 citations
TL;DR: Recent computational and structural biology studies of evolutionary accretion that make use of the ideographic and nomothetic scientific frameworks are reviewed, making explicit the need to understand processes of molecular growth and information transfer of macromolecules.
Abstract: Accretion occurs pervasively in nature at widely different timeframes The process also manifests in the evolution of macromolecules Here we review recent computational and structural biology studies of evolutionary accretion that make use of the ideographic (historical, retrodictive) and nomothetic (universal, predictive) scientific frameworks Computational studies uncover explicit timelines of accretion of structural parts in molecular repertoires and molecules Phylogenetic trees of protein structural domains and proteomes and their molecular functions were built from a genomic census of millions of encoded proteins and associated terminal Gene Ontology terms Trees reveal a ‘metabolic-first’ origin of proteins, the late development of translation, and a patchwork distribution of proteins in biological networks mediated by molecular recruitment Similarly, the natural history of ancient RNA molecules inferred from trees of molecular substructures built from a census of molecular features shows patchwork-like accretion patterns Ideographic analyses of ribosomal history uncover the early appearance of structures supporting mRNA decoding and tRNA translocation, the coevolution of ribosomal proteins and RNA, and a first evolutionary transition that brings ribosomal subunits together into a processive protein biosynthetic complex Nomothetic structural biology studies of tertiary interactions and ancient insertions in rRNA complement these findings, once concentric layering assumptions are removed Patterns of coaxial helical stacking reveal a frustrated dynamics of outward and inward ribosomal growth possibly mediated by structural grafting The early rise of the ribosomal ‘turnstile’ suggests an evolutionary transition in natural biological computation Results make explicit the need to understand processes of molecular growth and information transfer of macromolecules
27 citations