Substance P - Structural Features and Regulatory Functions

Abstract Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions—angiogenesis, fibroblast proliferation, and stimulation of BM progenitors—are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 ±12 vs 18 ±3; P < .01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research.

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Photoaffinity Labeling of Mutant Neurokinin-1 Receptors Reveals Additional Structural Features of the Substance P/NK-1 Receptor Complex†

Biochemistry ◽

10.1021/bi001880x ◽

2001 ◽

Vol 40 (8) ◽

pp. 2530-2539 ◽

Cited By ~ 23

Author(s):

Douglas Macdonald ◽

Dale F. Mierke ◽

Hanzhong Li ◽

Maria Pellegrini ◽

Bruce Sachais ◽

...

Keyword(s):

Substance P ◽

Photoaffinity Labeling ◽

Structural Features ◽

Receptor Complex ◽

Neurokinin 1

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Deep evolutionary analysis reveals the design principles of fold A glycosyltransferases

10.1101/2019.12.31.891697 ◽

2019 ◽

Author(s):

Rahil Taujale ◽

Aarya Venkat ◽

Liang-Chin Huang ◽

Wayland Yeung ◽

Khaled Rasheed ◽

...

Keyword(s):

Structural Features ◽

Model Organisms ◽

Evolutionary Information ◽

Evolutionary Analysis ◽

Cellular Functions ◽

Learning Classifier ◽

Donor And Acceptor ◽

Complex Relationships ◽

Functionally Diverse ◽

Regulatory Functions

AbstractGlycosyltransferases (GTs) are prevalent across the tree of life and regulate nearly all aspects of cellular functions by catalyzing synthesis of glycosidic linkages between diverse donor and acceptor substrates. Despite the availability of GT sequences from diverse organisms, the evolutionary basis for their complex and diverse modes of catalytic and regulatory functions remain enigmatic. Here, based on deep mining of over half a million GT-A fold sequences from diverse organisms, we define a minimal core component shared among functionally diverse enzymes. We find that variations in the common core and the emergence of hypervariable loops extending from the core contributed to the evolution of catalytic and functional diversity. We provide a phylogenetic framework relating diverse GT-A fold families for the first time and show that inverting and retaining mechanisms emerged multiple times independently during the course of evolution. We identify conserved modes of donor and acceptor recognition in evolutionarily divergent families and pinpoint the sequence and structural features for functional specialization. Using the evolutionary information encoded in primary sequences, we trained a machine learning classifier to predict donor specificity with nearly 88% accuracy and deployed it for the annotation of understudied GTs in five model organisms. Our studies provide an evolutionary framework for investigating the complex relationships connecting GT-A fold sequence, structure, function and regulation.

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Isolation, localization, and cardiovascular activity of tachykinins from the stomach of the bowfin Amia calva

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.3.r565 ◽

1995 ◽

Vol 269 (3) ◽

pp. R565-R571 ◽

Cited By ~ 1

Author(s):

D. Waugh ◽

K. E. Groff ◽

B. Platzack ◽

J. H. Youson ◽

K. R. Olson ◽

...

Keyword(s):

Cardiac Output ◽

Amino Acid ◽

Substance P ◽

Vascular Resistance ◽

Structural Features ◽

Surface Epithelium ◽

Neurokinin A ◽

Cardiovascular Activity ◽

Gastric Glands ◽

Arterial Blood

The bowfin is an extant representative of an ancient group of ray-finned fish with evolutionary connections to modern teleosts. A peptide with substance P-like immunoreactivity was isolated from an extract of bowfin stomach and its primary structure was established as Ser-Lys-Ser-His-Gln-Phe-Tyr-Gly-Leu-Met-NH2. This amino acid sequence resembles mammalian substance P only in the COOH-terminal region of the peptide. A second tachykinin with neurokinin A-like immunoreactivity isolated from the extract comprises 23 amino acid residues and shows limited structural similarity to mammalian neuropeptide-gamma. A randomly distributed population of cells in the gastric glands of the bowfin were immunostained with an antiserum raised against substance P, but no immunopositive structures were identified in the surface epithelium, lamina propria, or the nerve plexuses of the submucosa. Bolus injections of synthetic bowfin substance P (0.1-10 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in a significant and dose-dependent rise in vascular resistance and arterial blood pressure (P < 0.01) and a fall in cardiac output (P < 0.05) without change in heart rate. After 5-10 min, arterial pressure and vascular resistance returned to preinjection levels, but cardiac output significantly (P < 0.05) increased over baseline values. The response to the peptide was unaffected by pretreatment of the animals with phentolamine. The study has shown that the stomach of the bowfin synthesizes tachykinins with novel structural features that display cardiovascular activity in this species.

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RsmC of Erwinia carotovora subsp. carotovora Negatively Controls Motility, Extracellular Protein Production, and Virulence by Binding FlhD and Modulating Transcriptional Activity of the Master Regulator, FlhDC

Journal of Bacteriology ◽

10.1128/jb.00154-09 ◽

2009 ◽

Vol 191 (14) ◽

pp. 4582-4593 ◽

Cited By ~ 16

Author(s):

Asita Chatterjee ◽

Yaya Cui ◽

Arun K. Chatterjee

Keyword(s):

Differential Susceptibility ◽

Erwinia Carotovora ◽

Structural Features ◽

Extracellular Proteins ◽

Negative Regulator ◽

Master Regulator ◽

Global Regulators ◽

Extracellular Protein Production ◽

Regulatory Functions ◽

First Time

ABSTRACT RsmC and FlhDC are global regulators controlling extracellular proteins/enzymes, rsmB RNA, motility, and virulence of Erwinia carotovora subsp. carotovora. FlhDC, the master regulator of flagellar genes, controls these traits by positively regulating gacA, fliA, and rsmC and negatively regulating hexA. RsmC, on the other hand, is a negative regulator of extracellular proteins/enzymes, motility, and virulence since the deficiency of RsmC in FlhDC+ strain results in overproduction of extracellular proteins/enzymes, hypermotility, and hypervirulence. These phenotypes are abolished in an RsmC− FlhDC− double mutant. We show that RsmC interferes with FlhDC action. Indeed, the expression of all three targets (i.e., gacA, rsmC, and fliA) positively regulated in E. carotovora subsp. carotovora by FlhDC is inhibited by RsmC. RsmC also partly relieves the inhibition of hexA expression by FlhDC. The results of yeast two-hybrid analysis revealed that RsmC binds FlhD and FlhDC, but not FlhC. We propose that binding of RsmC with FlhD/FlhDC interferes with its regulatory functions and that RsmC acts as an anti-FlhD4FlhC2 factor. We document here for the first time that RsmC interferes with activation of fliA and motility in several members of the Enterobacteriaceae family. The extent of E. carotovora subsp. carotovora RsmC-mediated inhibition of FlhDC-dependent expression of fliA and motility varies depending upon enterobacterial species. The data presented here support the idea that differences in structural features in enterobacterial FlhD are responsible for differential susceptibility to E. carotovora subsp. carotovora RsmC action.

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Pivotal roles of PCNA loading and unloading on heterochromatin function

10.1101/232181 ◽

2017 ◽

Author(s):

Ryan Janke ◽

Grant King ◽

Martin Kupiec ◽

Jasper Rine

Keyword(s):

Dna Replication ◽

Transcriptional Silencing ◽

Structural Features ◽

S Phase ◽

Histone Chaperones ◽

Replication Forks ◽

Nucleosome Assembly ◽

Replication Machinery ◽

Loading And Unloading ◽

Regulatory Functions

ABSTRACTIn Saccharomyces cerevisiae, heterochromatin structures required for transcriptional silencing of the HML and HMR loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally-silent states of HML and HMR are successfully maintained throughout S-phase. Mutations of specific components of the replisome diminish the capacity to maintain silencing of HML and HMR through replication. Similarly, mutations in histone chaperones involved in replication-coupled nucleosome assembly reduce gene silencing. Bridging these observations, we determined that the PCNA unloading activity of Elg1 was important for coordinating DNA replication forks with the process of replication-coupled nucleosome assembly to maintain silencing of HML and HMR through S-phase. Collectively these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase.SIGNIFICANCE STATEMENTDNA replication poses a unique logistical challenge for the cell in that structural features of chromatin and their regulatory functions must be carefully coordinated with passage of replication machinery so faithful duplication of both the genome and its chromatin structures may be achieved. Nucleosome assembly is fundamental to reestablishment of chromatin in the wake of DNA replication, and here a mechanism by which nucleosome assembly is coordinated with DNA replication to maintain silenced chromatin is described.

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Electron microscopy and diffraction studies of polyimides

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074069 ◽

1983 ◽

Vol 41 ◽

pp. 28-29

Author(s):

O.C. de Hodgins ◽

K. R. Lawless ◽

R. Anderson

Keyword(s):

Electron Microscopy ◽

Electron Microscope ◽

Structural Features ◽

Inert Atmosphere ◽

Polyimide Films ◽

Resolution Electron ◽

The Matrix ◽

High Resolution Electron Microscope ◽

Diffraction Patterns ◽

Polymeric Samples

Commercial polyimide films have shown to be homogeneous on a scale of 5 to 200 nm. The observation of Skybond (SKB) 705 and PI5878 was carried out by using a Philips 400, 120 KeV STEM. The objective was to elucidate the structural features of the polymeric samples. The specimens were spun and cured at stepped temperatures in an inert atmosphere and cooled slowly for eight hours. TEM micrographs showed heterogeneities (or nodular structures) generally on a scale of 100 nm for PI5878 and approximately 40 nm for SKB 705, present in large volume fractions of both specimens. See Figures 1 and 2. It is possible that the nodulus observed may be associated with surface effects and the structure of the polymers be regarded as random amorphous arrays. Diffraction patterns of the matrix and the nodular areas showed different amorphous ring patterns in both materials. The specimens were viewed in both bright and dark fields using a high resolution electron microscope which provided magnifications of 100,000X or more on the photographic plates if desired.

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Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074768 ◽

1983 ◽

Vol 41 ◽

pp. 194-195

Author(s):

D. F. Blake ◽

L. F. Allard ◽

D. R. Peacor

Keyword(s):

High Resolution ◽

Marine Invertebrates ◽

Sea Urchins ◽

Structural Features ◽

Sea Stars ◽

High Resolution Tem ◽

Relationship Of ◽

The Relationship ◽

Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

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Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

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Measurement and Reduction of Radiation Damage in Frozen Hydrated Crystalline Specimens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069867 ◽

1978 ◽

Vol 36 (3) ◽

pp. 70-77 ◽

Cited By ~ 1

Author(s):

R.M. Glaeser ◽

S.B. Hayward

Keyword(s):

Diffraction Pattern ◽

Structural Information ◽

Structural Disorder ◽

Structural Features ◽

Biological Macromolecules ◽

Diffraction Intensity ◽

Object Structure ◽

Specimen Material ◽

Unit Cells ◽

Identical Unit

Highly ordered or crystalline biological macromolecules become severely damaged and structurally disordered after a brief electron exposure. Evidence that damage and structural disorder are occurring is clearly given by the fading and eventual disappearance of the specimen's electron diffraction pattern. The fading and disappearance of sharp diffraction spots implies a corresponding disappearance of periodic structural features in the specimen. By the same token, there is a oneto- one correspondence between the disappearance of the crystalline diffraction pattern and the disappearance of reproducible structural information that can be observed in the images of identical unit cells of the object structure. The electron exposures that result in a significant decrease in the diffraction intensity will depend somewhat upon the resolution (Bragg spacing) involved, and can vary considerably with the chemical makeup and composition of the specimen material.

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