Current Protein & Peptide Science

ISSN: 1389-2042

Current Protein and Peptide Science
Volume 7, Number 1, February 2006

Contents


Editorial Pp.1


On the Existence of a Global Molecular Network Enmeshing the Whole Central Nervous System: Physiological and Pathological Implications Pp. 3-15
L.F. Agnati, E. Zunarelli, S. Genedani and K. Fuxe
[Abstract]


The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants Pp. 17-45
Andrea Bellelli, Maurizio Brunori, Adriana Erica Miele, Gianna Panetta and Beatrice Vallone
[Abstract]


Expression of Highly Toxic Genes in E. coli: Special Strategies and Genetic Tools Pp. 47-56
F. Saïda, M. Uzan, B. Odaert and F. Bontems
[Abstract]


Recombinant Allergens for Diagnosis and Immunotherapy of Allergic Disorders, with Emphasis on Cockroach Allergy Pp. 57-71
Kyoung Yong Jeong, Chein-Soo Hong and Tai-Soon Yong
[Abstract]


Survey of Functional Activities of Alpha-fetoprotein Derived Growth Inhibitory Peptides: Review and Prospects Pp. 73-100
Gerald J. Mizejewski and George Butterstein
[Abstract]




Abstracts

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Editorial

I am very pleased to announce that CURRENT PROTEIN and PEPTIDE SCIENCE has achieved an impact factor of 3.00 for the past year. This is an increase from the previous rating of 1.79. Clearly, the quality of papers published in the journal has increased and we are very grateful to the authors who have contributed their best work to this review forum. We strongly believe that the reviews published here are providing an excellent way to encapsulate recent scientific progress and an outstanding stimulus to new experimentation to move the field of protein and peptide science forward.

Volume 6 had three special “Hot Topics” issues: Host Defense Peptides, edited by Alessandro Tossi, Exploiting the Peptide Pool; New Structures, Novel Functions and Therapeutic Opportunities, edited by Knut Adermann, and Biomedicine and Bioinformatics, edited by Kuo-Chen Chou. These three issues highlight the diversity of the protein and peptide world, with topics from naturally-occurring peptides, through synthetic chemistry, and into the emerging world of bioinformatics. Together with three issues that featured general topics of great importance, Volume 6 has taken CURRENT PROTEIN and PEPTIDE SCIENCE to new heights. We expect that Volume 7 will continue this trend.

In the coming year, Bentham Science Publishing will improve the mechanism for manuscript submission, assignment to referees, and communication to authors. This will improve the processing of manuscripts and thus shorten the time between submission and publication. As always, we are continually seeking new Guest Editors to organize special Hot Topics issues and welcome suggestions from our readers for topics. At the same time, we will continue to publish stand-alone papers on topics submitted by individuals. It has been a great pleasure to work with many scientists from around the world on papers for CURRENT PROTEIN and PEPTIDE SCIENCE and I look forward to working with many new authors in the future.

Ben M. Dunn
Editor-in Chief
Current Protein and Peptide Science


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On the Existence of a Global Molecular Network Enmeshing the Whole Central Nervous System: Physiological and Pathological Implications
L.F. Agnati, E. Zunarelli, S. Genedani and K. Fuxe

Proteins are endowed with the “Lego property”, i.e., the capability of steric fitting with other proteins to form high molecular weight complexes with emergent functions. These interactions may occur both as horizontal molecular networks at the plasma membrane level and as vertical molecular networks, i.e., towards the extra- and/or intracellular side of the cell. The present paper broadens this view by proposing the existence of three dimensional molecular net-works, mainly made by proteins and carbohydrates, which might interact with each other at boundaries of compartments such as plasma membranes to form a “global molecular network” (GMN) that pervades the intra- as well as the extra-cellular environment of the entire central nervous system. The GMN is a potentially plastic structure regulated through several means. For example, its extra-cellular part is under the remodeling action of the matrix metalloproteinases.

The proposal of a GMN has physiological and pathological implications. In primis, classical synaptic transmission, gap junctions and volume transmission signals by modulating GMN could importantly contribute to the “binding phenome-non”, i.e. the phase synchronization of firing rates in far-located neuronal cortical groups. Secondly, alterations in pro-tein conformation could alter the GMN organization and hence the neuronal network morphology and function. This could lead to the formation of abnormal protein aggregates such as amyloid plaques and neurofibrillary tangles, which, in turn, might affect the GMN function and/or the reciprocal interactions between its parts especially at the boundaries between compartments.


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The Allosteric Properties of Hemoglobin: Insights from Natural and Site Directed Mutants
Andrea Bellelli, Maurizio Brunori, Adriana Erica Miele, Gianna Panetta and Beatrice Vallone

After over a century of extensive research, hemoglobin has become the prototype of allosteric and cooperative proteins. Its molecular structure, known in great detail, has allowed the design of hundreds of site directed mutations, aimed at interfering with its function, and thus at testing our hypotheses on the molecular mechanisms of allostery. The wealth of information thus obtained is difficult to read except for specialists, not only because it makes use of many different technical approaches, but also because of its intrinsically patchy nature. Moreover, several researchers have tried to assign specific roles to segments of the polypeptide chains, rather than to single residues, and have tested their hy-potheses by multiple point mutations or by complete replacement with the homologous segment from a different hemo-globin to produce chimeric macromolecules. This approach is in great need of a revision since putative functionally rele-vant segments partially overlap. This review briefly describes the structure and function of hemoglobin, and analyzes the effect of point mutations, multiple mutations and segment replacement, with special attention to possible biotechnologi-cal applications, ranging from pharmacology (Hb solutions as resuscitating fluids and sources of the protein found in hemoglobinopathies for biochemical studies) to bioreactors. Occasional reference is made to site directed mutants of myoglobin, whenever this helps clarifying perplexing results obtained on hemoglobin.


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Expression of Highly Toxic Genes in E. coli: Special Strategies and Genetic Tools
F. Saïda, M. Uzan, B. Odaert and F. Bontems

Escherichia coli (E. coli) remains the most efficient widely-used host for recombinant protein production. Well-known genetics, high transformation efficiency, cultivation simplicity, rapidity and inexpensiveness are the main factors that contribute to the selection of this host. With the advent of the post-genomic era has come the need to express in this bacterium a growing number of genes originating from different organisms. Unfortunately, many of these genes severely interfere with the survival of E. coli cells. They lead to bacteria death or cause significant defects in bacteria growth that dramatically decrease expression capabilities. In this paper, we review special strategies and genetics tools successfully used to express, in E. coli, highly toxic genes. Suppression of basal expression from leaky inducible promoters, suppression of read-through transcription from cryptic promoters, tight control of plasmids copy numbers and proteins production as inactive (but reversible) forms are among the solutions presented and discussed. Special expression vectors and modified E. coli strains are listed and their effectiveness illustrated with key examples, some of which are related to our study of the highly toxic phage T4 restriction endoribonuclease RegB. We mainly selected those strategies and tools that permit E. coli normal growth until the very moment of highly toxic gene induction. Expression then occurs efficiently before cells die. Because they do not target a particular toxic effect, these strategies and tools can be used to express a wide variety of highly toxic genes.


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Recombinant Allergens for Diagnosis and Immunotherapy of Allergic Disorders, with Emphasis on Cockroach Allergy
Kyoung Yong Jeong, Chein-Soo Hong and Tai-Soon Yong

The prevalence of allergic disorders has increased over the past few decades and the quality of life has been significantly influenced at least for the allergic subjects. Allergen avoidance is thought to be the best way of preventing clinical manifestation of the disease, however, it is not possible for some allergens, and other pharmacological and/or immunological treatment has to be made. Repetitive injection of sensitized allergens to the patients (immunotherapy) is the only known curative approach to the disease even though the exact mechanism is not clear to date. Crude extract of allergens has lots of shortcomings which might arouse unexpected results. Genetic engineering and recombinant aller-gens are thought to be one of the alternative ways to overcome these limitations. Genetic engineering could facilitate the investigation of immune responses of the subjects especially on B cell and T cell epitopes, and produce the therapeutic allergens which might minimize the possible side effects. Furthermore, conjugation of immuno-modulatory molecules such as CpG-ODN, cytokines, or toxins which could act specifically to the given allergens, and maleylation of the aller-gens could maximize the prophylactic or therapeutic effect.

Immunotherapies for the pollen allergy and insect sting allergy have been thought to be successful. House dust mite al-lergy and cockroach allergy have been reported less beneficial by immunotherapeutic approaches. Cockroaches are one of the most important causes of asthma, and severe complications are often reported in the children in city dwellers with low-incomes. The studies of the biological functions of cockroach allergens and the use of recombinant allergens should allow understanding of mechanisms of cockroach-elicited allergic disorders and development of allergen-specific and sensitive diagnostics and tailored therapeutic approaches in the future.


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Survey of Functional Activities of Alpha-fetoprotein Derived Growth Inhibitory Peptides: Review and Prospects
Gerald J. Mizejewski and George Butterstein

Alpha-fetoprotein (AFP), known largely as a growth-promoting agent, possesses a growth-inhibitory motif recently identified as an occult epitopic segment in the third domain. The present study reviews the multiple biological activities of this AFP-derived peptide segment termed the Growth Inhibitory Peptide (GIP), which is a 34-amino acid fragment taken directly from the full-length 590 amino acid molecule. The GIP segment has been chemically synthesized, purified, characterized, and subjected to a variety of bioassays. The GIP has a proven record of growth suppression in both fetal and tumor cells, but not in normal adult cells. Even though the mechanism of action has not been completely elucidated, GIP participates in various biological activities such as endocytosis, angiogenesis, and cytoskeleton-induced/cell shape changes. In this review, a survey of the functional roles of the GIP is presented which encompasses multiple organizational levels of GIP involvement, including the 1) organism, 2) organ, 3) tissue, 4) cell, 5) plasma membrane, 6) cytoplasm, and 7) the nucleus. At the cell membrane interface, the actions of GIP are discussed concern-ing cell aggregation, agglutination, adhesion, and migration in light of GIP serving as a possible decoy ligand and/or soluble receptor. Regarding cytosolic activities, GIP has been reported to inhibit various cytoplasmic enzyme activities, modulate apoptotic events, and regulate cytoplasmic signal transduction (MAP kinase) cascades. Concerning the nuclear compartment, GIP is capable of complexing with the estrogen receptor and binding estradiol, but does not affect estra-diol-induced estrogen receptor transcription. In overview, efforts were made to review the multiple biological activities reported for GIP in order to prioritize likely physiological activities and present an updated consensus of functional roles for this AFP-derived peptide.