PROTEOMICS Cellular proteins and peptides E-Book

Fernando Fussi

• Herausgeber: Fernando Fussi
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2013

Beschreibung

SummaryThe book, divided in 16 Sections, classifies and describes the properties of the numberless proteins and peptides constituting the main portion of the living cells. A special attention is devoted to peculiar arguments, as:genome structure, mutations and mutagens, gene repair and apoptosis, gene manipulation (Sect.1);analysis and synthesis of peptides and polynucleotides (Sect.2);simple and conjugate proteins, visual cycle, circadian clocks, heme proteins (Sect.3);carrier proteins, proteases and inhibitors, factors of haemostasis and fibrinolysis (Sect.4);collagens, keratins, proteoglycans (Sect.5);adhesion proteins and ligands, spermatogenesis, fertilization (Sect.6);structural proteins, cytoskeleton components, contractile systems (Sect.7);innate and adaptative immunity, antigens and antibodies, T and B effectors, cytotoxio mechanisms, the inflammatory response (Sect.8);growth factors, stem cells and reprogramming, embryogenic and morphogenic proteins, neurotrophic factors, chaperonins (Sect.9);ion channels, transporters, tcxins and animal neurotoxins (Sect.10);translocation, transmembrane channels, vesicle formation and endo-exocytosis (Sect.11);short range messengers (cytokines): interleukins, tumor necrosis factor family, interferons (Sect.12);long distance messengers: peptidic and proteic hormones (Sect.13);synaptic transmission, neuropeptides, neurotransmitters and neuroreceptors, molecular basis of memories, appraisal, cognition, mood, and their disturbances (Sect.14);biochemistry of signal transduction: first and second messengers, signaling receptors and cyclases, G proteins and GTPases, phosphorylative modulation and protein kinases, other enzymatically driven intracellular regulations (Sect.15);virus structure and classification, phagi, episomes, plasmids, viral diseases, prions, protein conformation-dependent diseases, dementias (Sect.16);Trends in cancer pharmacological therapy (App.B);Some nuclear transcription factors (App.C).

Leseprobe

Fernando Fussi

PROTEOMICS

Cellular proteins and peptides

PROTEOMICSCellular proteins and peptides

Fernando Fussi

Edizione digitale: giugno 2013

ISBN: 9788868550349

Edizione digitale realizzata da Simplicissimus Book Farm srl

Contents

Section 1.  Genes and Proteins. Introduction to genetic engineering

1.1  Genes and genome

1.2  Genome structure

1.3  Some chemical and physical properties of DNA

1.4  Spontaneous and induced mutations. Mutagens

1.4.1  Chromosome aberrations

1.5  Cellular and viral oncogenes

1.6  Cell cycle and cycle block

1.6.1  Kinases involved in cell cycle

1.6.2  Players and regulators in the mitotic program

1.6.3  Meiosis and germ line specification regulators

1.7  Repair processes, aging, apoptosis

1.7.1  Commitment

1.7.2  Transduction

1.7.3  Modulation

1.7.4  Execution

1.8  Gene regulation

1.8.1  Nuclear Receptors and Development

1.9  Replication and Transcription

1.10  Translation of the genetic message

1.11  Post-transcriptional events

1.11.1  mRNA elaboration

1.11.2  Conjugation

1.11.3  Shaping

1.11.4  Assembly

1.11.5  Splitting

1.11.6  Modulation

1.12  Introduction to gene manipulation

1.12.1  Gene isolation

1.12.2  Inserting a gene into a vector

1.12.3  Introducing a transformed vector into bacteria

1.12.4  Cloning

1.12.4  Induction

Section 2.  Analysis and Synthesis of peptides and polynucleotides

2.1  Peptide and protein analysis

2.2  Peptide synthesis

2.3  Polynucleotide analysis

2.4  Polynucleotide synthesis

Section 3.  Simple and Conjugate Proteins

3.1  General protein structure

3.2  Glycoproteins

3.3  Lipoproteins

3.4  Nucleoproteins

3.5  Phosphoproteins

3.6  Prosthetic groups in conjugate proteins

3.7  Visual cycle

3.7.1  Circadian clocks

3.8  Heme proteins

Section 4.  Plasma proteins

4.1  Carrier proteins

4.1.1  Plasma lipoproteins

4.2  Proteases and protease inhibitors

4.2.1  Proteases

4.2.2  Protease inhibitors

4.3  Vasoactive peptides

4.4  Factors of hemostasis and coagulation

4.4.1  Platelet factors

4.4.2  Tissue factors

4.4.3  Plasma factors

4.5  Factors of fibrinolysis

4.6  Acute phase factors

Section 5.  Extracellular matrix components

5.0  Generalities

5.1  Collagens and elastin

5.2  Keratins

5.3  Proteoglycans

5.4  Adhesion proteins of the matrix

Section 6.  Cell Adhesion Molecules (CAM)

6.0  Adhesion proteins

6.1  Lectins and selectins

6.2  Integrins and integrin ligands

6.3  Selectin ligands

6.4  Immunoglobulins

6.5  Cadherins and catenins

6.6  Metallo proteases with disintegrin domains

6.6.1  Spermatogenesis and fertilization

Section 7.  Intracellular structural proteins

7.1  Cytoskeleton components

7.1.1  Microfilaments

7.1.2  Microtubules

7.1.3  Intermediate filaments

7.2  Membrane-cytoskeleton interactions

7.3  Contractile systems and muscle proteins

7.4  Adaptor proteins

Section 8.  Factors of the immunity

8.0  The immune response

8.1  Factors of the specific immunity: the antigens

8.2  From antigen to antibody

8.3  The Major Hystocompatibility Complex

8.4  Antibodies

8.5  Complement System

8.6  Cytotoxic mechanisms

8.6.1  Other factors of the innate immunity

8.7  Phagocytosis

8.8  The inflammatory response

Section 9.  Growth and shape mediators

9.0  Generalities on Growth Factors-induced signaling

9.1  Growth Factors

9.1.1  Pleiotropic growth factors and angiogenesis

9.1.2  Stem cells

9.1.3  Reprogramming

9.1.4  Mitogenic factors and early development

9.1.5  Spatial orientation in embryogenesis and morphogenic proteins

9.1.6  Chemotaxis

9.1.7  Neurotrophic factors

9.2  Chaperonins and heat shock proteins

Section 10.  Ion channels and Transporters

10.0  Generalities on Transporters

10.0.1  General features on ionophores

10.1  Potassium channels

10.2  Sodium channels and proton pumps

10.3  Calcium channels

10.4  Stretch-sensitive and ligand-operated cation channels

10.5  Porins and chloride channels

10.6  Toxins.  Neurotoxins affecting ion channels

10.6.1  Presynaptic neurotoxins affecting Na channels

10.6.2  Presynaptic neurotoxins affecting K channels

10.6.3  Presynaptic neurotoxins affecting Ca channels

Section 11.  Protein traslocation across membranes

11.0  Translocation

11.1  Transmembrane channels

11.1.1  Nuclear transport

11.2  Endocytosis and exocytosis

11.2.1  Endo- and exocytosis of synaptic vesicles

11.3  Transport through microtubules

Section 12.  Short Range Messengers

12.0  Cytokines

12.1  Interleukines

12.2  Tumor Necrosis Factor family

12.3  Chemokines

12.4  Colony Stmulating Factors

12.5  Interferons

Section 13.  Proteins and Peptides with Hormonal Activity

13.0  Hormones and substances with hormonal activity

13.1  Thymus hormones

13.2  Hormones from hypothalamus

13.3  Adeno-hypophyseal hormones

13.3.1  Pro-opiomelanocortin derivatives

13.3.2  Gonadotrophins

13.3.3  Somatotropic Hormone family

13.4  Hormones of neurohypophysis

13.5  Thyroid and parathyroid hormones in Ca regulation

13.6  Gastro-intestinal hormones active also in nervous system

13.6.1  Adipokines of adipose tissue

13.7  Pancreas hormones

13.8  Renal hormones

Section 14.  Neuropeptides, Neurotransmitters, Neuroreceptors

14.0  Synaptic transmission and neuropeptides

14.1  Neuropeptides associated to neurotransmitters

14.2  Neuroreceptors

14.2.1  Cathecolamine receptors

14.2.2  Acetylcholine receptors

14.2.3  Biogenic amine receptors

14.2.4  Aminoacid receptors

14.2.5  Neuropeptide receptors

14.3  Relations among endocrine, immunitary, nervous systems

14.4  Molecular basis of appraisal

14.4.1  A psychiatric approach to cognition and mood

Section 15.  Biochemistry of Signal Transduction

15.1  First messengers and their Receptors

15.2  Guanine nucleotide-binding proteins

15.3  Signal receptors and their messengers

15.4  Phosphorylative modulation

Section 16.  Viral proteins and Prions

16.1  Viruses

16.2  Phagi and Plasmids. Lysogeny and Proviruses

16.3  Prions and protein conformation-dependent diseases

16.3.1  Hereditary and sporadic dementias

Appendix A.  A list of diseases considered in this Guide

Appendix B.  Trends in cancer research and pharmacological therapies

Appendix C.  Further observations on some Nuclear Transcription Factors and related genes.

General Index.

Literature is at the end of each Section. Except for few exceptions, bibliography preceding 90ties is not cited.

List of Tables

1.1   Triplet (codon) meaning

1.2   Factors involved in apoptotic pathway

1.3A From signals to STAT-regulated nuclear effectors

1.3B Gene activation sequence

2.1   Polymerase Chain Reaction and DNA sequencing

3.1   International classification of enzymes

4.1   Plasma proteins according to electrophoretic mobility

4.3   Proteases and protease inhibitors

5.1   Antibiotics and mechanism of action

6.1   Cell adhesion molecules

6.2   Lectins, agglutinins

8.0   Surface antigens

8.1   T helpers (TH) from naïve CD4+ T cells

8.2   Antibodies

8.3   Mediators of inflammatory processes

9.1   Main growth factors, receptors and signaling modules

10.1  Animal toxins

12.1  Interleukins

13.1  Naturally occurring hormonal peptides in production and use

14.1  Neuropeptide co-localization with classical neurotransmitters

15.1  Some representative protein kinases in normal cells of vertebrates

16.1  LTH virus classification

App. B Antineoplastic drugs

List of Figures

1.1  Complementary base pairing.

1.2  Gene activation and transcription factors.

1.3  Inserting a gene into a vector.

2.1  Peptidic bond specific splitting.

2.2  Edman’s sequential degradation in solid phase.

2.3  Solid-phase peptide synthesis.

2.4  Solid-phase polynucleotide synthesis.

4.1  Kallikrein/kinin system.

4.2  Hemocoagulation.

4.3  Fibrinolysis.

7.1  Sarcomere structure.

8.1  IgG structure and Ig-related genes.

8.2  Complement activation.

13.1  Active sequences in pro-opiomelanocortin (POMC).

13.2  Sequence comparison in hormonal peptides.

15.1  Epinephrine-induced glycogenolysis activation and glycogenesis inhibition.

Aknowledgements

We wish to thank Dr. Aldo Del Maschio, Dr. Sandra Bertani, Katia Puhach, and my wife Maria Stella for technical assistance and revision of the contents. Dr Olindo Guerrini reviewed the draft and now, from the heaven, is very pleased for the results.

1

Genes and Proteins. Introduction to genetic Engineering

1.1 Genes and genome

Gene1 is the unit of inheritance and the unit of genetic information, made by polynucleotide sequences. The totality of individual genes constitutes the genome. Genes in humans, intended as tracts of DNA that can be transcribed in the final mRNA and further translated in proteins, constitute as little as 5 percent of the genomic DNA. Human genome has been sequenced in the late ‘90s. The most impactant surprise was that only about 23 000 genes – about the same number of Drosophila melanogaster and the plant Arabidopsis, barely more than the 1000 cells-formed worm Caenorhabditis elegans, half than the rice, Oryza saliva, about 10 000 less than water flea – are contained in the 5.5 billion base pairs that make up human DNA. So few coding genes (less than 2 percent of the entire human genome) codify for the program to build up about 90 000 estimated proteins, including the proteins that regulate gene functions, metabolism, signaling, cell division, defense. Most of the remaining non-coding nuclear DNA in eukaryotes is occupied by diverse families of repeats (introns see 1.11, mobile elements see 1.4, and large intergenic regions), including arrays of apparently “non-specific” satellite sequences and transposons (see 1.4) that constitute the “epigenetic elements” of the genome (see 1.8). Introns (see 1.11), non-codifying sequences inside genes, account for about one third of the human genome. A large part of formally called “non-coding” DNA is devoted to codify for regulatory RNA. Promoters (see 1.8) are DNA segments located at the head of genes. Pseudogenes (see 4.1) are inactive genes originated from the original ones by mutations, duplication, processing or retrotransposition (see 1.4). Their number in genome is quoted about the same as the codifying genes. Pseudogenes generate small RNAs (sRNA, see 1.8 and 8.0) that have regulatory functions. MicroRNA (mRNAs), see 1.8, are small, non coding genes that are found in the genomes of most eukaryotes, where they play an important role in gene expression regulation.

Regulatory proteins, RNA (including sRNAs, see 1.8), non-coding bits of DNA, even chemical and structural alterations of the genome itself control how, where, and when genes are expressed. Alternate splicing (see 1.11) and other post-transcriptional events multiply the potential number of proteins that a single gene may transcribe.

The body’s complete set of proteins corresponding to the genome sequence is defined proteome, and proteomics is the branch of biology that studies the proteins in a cell or tissue.

In eukaryotic cells, genome is contained in a nucleus surrounded by cytoplasm. Prokaryotic cells have no nuclei to contain the genome.

Based on genome structure, living beings are distinct in three categories:

•  VIRUSES: the viral genome is a single-or double-stranded DNA or RNA, with few tenths of genes. Replication depends on the mechanisms of the host cell. Phagi are viruses replicating in bacteria, with linear double-stranded DNA.

•  PROKARYOTES: possess only one circular chromosome formed by a double-helix DNA, normally in aploid state, without dominant or recessive genes. Bacterial DNA occupies the central part of the bacterial cell, referred to as the nucleoid, and is associated to nucleoid-associated proteins (NAPs) that perform two major functions: gene regulation and chromosome organization. Reproduction is generally asexuate, operated by cell division (mitosis). Genes are few thousands. Nucleus and mitochondria are absent. Some circular, extrachromosomal DNA can be found in cytoplasm. These ring structures are called plasmids. Bacterial genomes have intronless coding regions aligned almost contiguously along the chromosome. Pseudogenes (nonfunctional genes), lateral gene transfer regions, and transposable elements may be present. According to genome size, a distinction in free living bacteria (5-10 Mbases), recent or facultative pathogens (2-5 Mb), and obligate symbionts or pathogens (2-5 Mb) can be made.

•  EUKARYOTES: have a genome distributed in many chromosomes. In Caenorhabditis elegans, a six-chromosome nematode whose genome has been fully sequenced2, 97 × 106 bases are present, codifying for over 19 000 genes.

Somatic cells are generally diploids, germinal cells are in aploid state. Each gene may exist in several alternate forms, or alleles. By mating, alleles from maternal and paternal origin are recombined in diploid arrangement. The genetic constitution of an organism marks the genotype which is responsible for creating the phenotype. Reproduction is generally sexuated with gene recombination (meiosis). Meiosis is a type of cell division that reduces the double set of chromosomes (diploid state of alleles in eukaryotes) to a single set (aploid state), as observed in germinal cells (see 1.6 under “Meiosis and germ...”).

Gene recombination is distinct in several forms:

•  Crossing-over or general recombination allows favorable and unfavorable mutations to be separed, providing a mean to escape and to spread over for favorable alleles;

•  Conservative or site-specific recombination is responsible for the integration of a phagic genome into bacterial chromosomes;

•  Replicative recombination is related to the ability of certain genome elements to move from one location to another (transposable elements in bacteria).

Gene recombination is normal in eukaryotes and exceptional in prokaryotes, in which three recombination mechanisms are possible: