scholarly journals Exploring the Nature of Desmosomal Cadherin Associations in 3D

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Gethin R. Owen ◽  
David L. Stokes
Keyword(s):  
Electron Tomography ◽  
Three Dimensional ◽  
Direct Consequence ◽  
Desmosomal Cadherins ◽  
Protein Molecules ◽  
Structural Interactions ◽  
Structural Differences ◽  
Physical Principles ◽  
Insight Into

Desmosomes are a complex assembly of protein molecules that mediate adhesion between adjacent cells. Desmosome composition is well established and spatial relationships between components have been identified. Intercellular cell-cell adhesion is created by the interaction of extracellular domains of desmosomal cadherins, namely, desmocollins and desmogleins. High-resolution methods have provided insight into the structural interactions between cadherins. However, there is a lack of understanding about the architecture of the intact desmosomes and the physical principles behind their adhesive strength are unclear. Electron Tomography (ET) studies have offered three-dimensional visual data of desmosomal cadherin associations at molecular resolution. This review discusses the merits of two cadherin association models represented using ET. We discuss the possible role of sample preparation on the structural differences seen between models and the possibility of adaptive changes in the structure as a direct consequence of mechanical stress and stratification.

scholarly journals The distribution of myosin II in Dictyostelium discoideum slug cells.

1991 ◽  
Vol 115 (5) ◽  
pp. 1267-1274 ◽  
Author(s):  
S Eliott ◽  
P H Vardy ◽  
K L Williams
Keyword(s):  
Cell Motility ◽  
Dictyostelium Discoideum ◽  
Immunofluorescence Microscopy ◽  
Molecular Genetic ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Homogeneous Distribution ◽  
Multicellular Development ◽  
Insight Into

While the role of myosin II in muscle contraction has been well characterized, less is known about the role of myosin II in non-muscle cells. Recent molecular genetic experiments on Dictyostelium discoideum show that myosin II is necessary for cytokinesis and multicellular development. Here we use immunofluorescence microscopy with monoclonal and polyclonal antimyosin antibodies to visualize myosin II in cells of the multicellular D. discoideum slug. A subpopulation of peripheral and anterior cells label brightly with antimyosin II antibodies, and many of these cells display a polarized intracellular distribution of myosin II. Other cells in the slug label less brightly and their cytoplasm displays a more homogeneous distribution of myosin II. These results provide insight into cell motility within a three-dimensional tissue and they are discussed in relation to the possible roles of myosin II in multicellular development.

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

scholarly journals Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis

2021 ◽  
Vol 118 (10) ◽  
pp. e2019220118
Author(s):  
Benjamin Pluvinage ◽  
Elizabeth Ficko-Blean ◽  
Ilit Noach ◽  
Christopher Stuart ◽  
Nicole Thompson ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Peptide Bond ◽  
Molecular Organization ◽  
Dimensional Structure ◽  
Carbohydrate Binding ◽  
Functional Roles ◽  
Protein Substrates ◽  
Individual Domain ◽  
Insight Into

A challenge faced by peptidases is the recognition of highly diverse substrates. A feature of some peptidase families is the capacity to specifically use post-translationally added glycans present on their protein substrates as a recognition determinant. This is ultimately critical to enabling peptide bond hydrolysis. This class of enzyme is also frequently large and architecturally sophisticated. However, the molecular details underpinning glycan recognition by these O-glycopeptidases, the importance of these interactions, and the functional roles of their ancillary domains remain unclear. Here, using the Clostridium perfringens ZmpA, ZmpB, and ZmpC M60 peptidases as model proteins, we provide structural and functional insight into how these intricate proteins recognize glycans as part of catalytic and noncatalytic substrate recognition. Structural, kinetic, and mutagenic analyses support the key role of glycan recognition within the M60 domain catalytic site, though they point to ZmpA as an apparently inactive enzyme. Wider examination of the Zmp domain content reveals noncatalytic carbohydrate binding as a feature of these proteins. The complete three-dimensional structure of ZmpB provides rare insight into the overall molecular organization of a highly multimodular enzyme and reveals how the interplay of individual domain function may influence biological activity. O-glycopeptidases frequently occur in host-adapted microbes that inhabit or attack mucus layers. Therefore, we anticipate that these results will be fundamental to informing more detailed models of how the glycoproteins that are abundant in mucus are destroyed as part of pathogenic processes or liberated as energy sources during normal commensal lifestyles.

Pituitary blood flow

1982 ◽  
Vol 243 (6) ◽  
pp. E427-E442 ◽  
Author(s):  
R. B. Page
Keyword(s):  
Blood Flow ◽  
Median Eminence ◽  
Three Dimensional ◽  
Vascular Anatomy ◽  
Flow Regulation ◽  
Organ Blood Flow ◽  
Regional Control ◽  
New Concepts ◽  
Insight Into

The direction of pituitary blood flow, the amount of pituitary blood flow, its regional control, and the role of the median eminence microcirculation are the subjects of this review. Present concepts of pituitary blood flow are focused almost entirely on its direction and arouse from studies of pituitary vascular anatomy performed almost 50 years ago. The development of new anatomic techniques has led to a reappraisal of pituitary angioarchitecture, stimulated physiological studies to clarify the pattern of blood flow within the entire gland, and led to a reappraisal of accepted concepts of directional pituitary blood flow. The availability of techniques to accurately measure organ blood flow has permitted study of pituitary blood flow; and, when combined with knowledge of pituitary anatomy, the application of these techniques promises to provide a means to develop insight into control of the mechanisms by which chemical messengers are delivered to the pituitary to control its function. New anatomic techniques promise to develop new understanding of the three-dimensional arrangement of median eminence microvasculature and yield new concepts of blood flow regulation within the median eminence that can be tested by physiological means.

scholarly journals Detailed structural and biochemical characterization of the nexin-dynein regulatory complex

2015 ◽  
Vol 26 (2) ◽  
pp. 294-304 ◽  
Author(s):  
Toshiyuki Oda ◽  
Haruaki Yanagisawa ◽  
Masahide Kikkawa
Keyword(s):  
Biochemical Characterization ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Dynein Motor ◽  
Cryo Electron Tomography ◽  
Regulatory Complex ◽  
And Function

The nexin-dynein regulatory complex (N-DRC) forms a cross-bridge between the outer doublet microtubules of the axoneme and regulates dynein motor activity in cilia/flagella. Although the molecular composition and the three-dimensional structure of N-DRC have been studied using mutant strains lacking N-DRC subunits, more accurate approaches are necessary to characterize the structure and function of N-DRC. In this study, we precisely localized DRC1, DRC2, and DRC4 using cryo–electron tomography and structural labeling. All three N-DRC subunits had elongated conformations and spanned the length of N-DRC. Furthermore, we purified N-DRC and characterized its microtubule-binding properties. Purified N-DRC bound to the microtubule and partially inhibited microtubule sliding driven by the outer dynein arms (ODAs). Of interest, microtubule sliding was observed even in the presence of fourfold molar excess of N-DRC relative to ODA. These results provide insights into the role of N-DRC in generating the beating motions of cilia/flagella.

Structure of a proteolytically resistant analogue of (NLys)5SFTI-1 in complex with trypsin: evidence for the direct participation of the Ser214 carbonyl group in serine protease-mediated proteolysis

2014 ◽  
Vol 70 (3) ◽  
pp. 668-675 ◽  
Author(s):  
Szymon Krzywda ◽  
Mariusz Jaskolski ◽  
Krzysztof Rolka ◽  
Maciej J. Stawikowski
Keyword(s):  
Hydrogen Bond ◽  
Carbonyl Group ◽  
Serine Proteases ◽  
Peptide Ligands ◽  
Protein Protein Interaction ◽  
Proteolytic Resistance ◽  
Structural Differences ◽  
Natural Inhibitor ◽  
Insight Into

Peptide–peptoid hybrids are found to be potent inhibitors of serine proteases. These engineered peptidomimetics benefit from both types of units of the biopolymeric structure: the natural inhibitor part serves as a good binding template, while the P1-positioned peptoid component provides complete resistance towards proteolysis. In this report, the mechanism of proteolytic resistance of a P1 peptoid-containing analogue is postulated based on the crystal structure of the (NLys)5-modified sunflower trypsin inhibitor SFTI-1 in complex with bovine trypsin solved at 1.29 Å resolution. The structural differences between the (NLys)5SFTI-1–trypsin complex and the native SFTI-1–trypsin complex are surprisingly small and reveal the key role of the carbonyl group of the Ser214 residue of the enzyme, which is crucial for binding of the inhibitor and plays a crucial role in proteolysis mediated by serine proteases. The incorporatedNLys5 peptoid residue prevents Ser214 from forming a hydrogen bond to the P1 residue, and in turn Gln192 does not form a hydrogen bond to the carbonyl group of the P2 residue. It also increases the distance between the Ser214 carbonyl group and the Ser195 residue, thus preventing proteolysis. The hybrid inhibitor structure reported here provides insight into protein–protein interaction, which can be efficiently and selectively probed with the use of peptoids incorporated within endogenous peptide ligands.

Crystal structure of the FAS1 domain of the hyaluronic acid receptor stabilin-2

2018 ◽  
Vol 74 (7) ◽  
pp. 695-701 ◽  
Author(s):  
Aleksandra Twarda-Clapa ◽  
Beata Labuzek ◽  
Dobroslawa Krzemien ◽  
Bogdan Musielak ◽  
Przemyslaw Grudnik ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cancer Metastasis ◽  
Potential Role ◽  
Three Dimensional ◽  
Protein Fragments ◽  
Acid Receptor ◽  
X Ray ◽  
Insight Into

Recent research has identified a potential role of the hyaluronic acid receptor stabilin-2 (Stab2) in cancer metastasis. Stab2 belongs to a group of scavenger receptors and is responsible for the clearance of more than ten ligands, including hyaluronic acid (HA). In vivo experiments on mice have shown that the absence of Stab2, or its blocking by an antibody, effectively opposes cancer metastasis, which is accompanied by an increase in the level of circulating HA. Knowledge of ligand recognition and signal transduction by Stab2 is limited and no three-dimensional structures of any protein fragments of this receptor have been solved to date. Here, a high-resolution X-ray structure of the seventh FAS1 domain of Stab2 is reported. This structure provides the first insight into the Stab2 structure.

scholarly journals Three-Dimensional Structures of the A, B, and CCapsids of Rhesus Monkey Rhadinovirus: Insights into GammaherpesvirusCapsid Assembly, Maturation, and DNAPackaging

2003 ◽  
Vol 77 (24) ◽  
pp. 13182-13193 ◽  
Author(s):  
Xue-Kui Yu ◽  
Christine M. O'Connor ◽  
Ivo Atanasov ◽  
Blossom Damania ◽  
Dean H. Kedes ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Three Dimensional ◽  
Model System ◽  
Electron Cryomicroscopy ◽  
Interacting Protein ◽  
Structural Differences ◽  
Dimensional Reconstruction ◽  
Capsid Maturation ◽  
First Time

ABSTRACT Rhesus monkey rhadinovirus (RRV) exhibits high levels of sequence homology to human gammaherpesviruses, such as Kaposi's sarcoma-associated herpesvirus, and grows to high titers in cell cultures, making it a good model system for studying gammaherpesvirus capsid structure and assembly. We have purified RRV A, B, and C capsids, thus for the first time allowing direct structure comparisons by electron cryomicroscopy and three-dimensional reconstruction. The results show that the shells of these capsids are identical and are each composed of 12 pentons, 150 hexons, and 320 triplexes. Structural differences were apparent inside the shells and through the penton channels. The A capsid is empty, and its penton channels are open. The B capsid contains a scaffolding core, and its penton channels are closed. The C capsid contains a DNA genome, which is closely packaged into regularly spaced density shells (25Å apart), and its penton channels are open. The different statuses of the penton channels suggest a functional role of the channels during capsid maturation, and the overall structural similarities of RRV capsids to alphaherpesvirus capsids suggest a common assembly and maturation pathway. The RRV A capsid reconstruction at a 15-Å resolution, the best achieved for gammaherpesvirus particles, reveals overall structural similarities to alpha- and betaherpesvirus capsids. However, the outer regions of the capsid, including densities attributed to the Ta triplex and the small capsomer-interacting protein (SCIP or ORF65), exhibit prominent differences from their structural counterparts in alphaherpesviruses. This structural disparity suggests that SCIP and the triplex, together with tegument and envelope proteins, confer structural and potentially functional specificities to alpha-, beta-, and gammaherpesviruses.

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