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Free Content Editorial [ Hot Topic:Protamines (Guest Editors: Monique Cosman Balhorn & Rod Balhorn)]

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The small, highly basic nuclear proteins called protamine that package DNA in the sperm of all mammals, most vertebrates and many plant species were discovered nearly 150 years ago. These amazing little proteins have been found to exhibit little structural or functional similarity to any other known chromatin or DNA binding protein. The protamines, which are categorized into two closely related families, protamine P1 and protamine P2, belong to a very limited class of proteins that remain unstructured in solution and do not adopt a conformation until they bind to their intended partner or target. When these proteins are expressed inside the maturing spermatid and delivered into the nucleus, the protamines bind along the entire length of the DNA, displace the majority of the bound chromatin proteins, and globally inactivate the entire elongating spermatid genome. Working in concert with a few remaining sperm specific histones and other proteins retained in sperm chromatin, the genome is deprogrammed and selected male genes are imprinted. This reorganization prepares the sperm genome so it will no longer function as a testis cell and provides a mechanism for the reactivation of a specific subset of genes early after fertilization. Clearly this is a lot of “functionality” to attribute to any protein. However, results from recent biophysical studies suggest the protamines may also perform another function that is not typical of other DNA binding proteins. Upon binding to DNA and condensing it into toroids, the formation of the toroid generates sufficiently large forces inside the nucleus to induce the collapse of the entire spermatid genome, condense the nucleus into a very small volume and perhaps even drive the shaping of the sperm head.

The papers presented in this special HOT TOPICS issue on Protamines: Structure and Function review and provide new information and insight into 1) how the protamine proteins evolved and the impact of these changes on chromatin organization, 2) the processing of the protamine P2 precursor and the relationship between incomplete P2 processing and male infertility, 3) the impact of altering the proportion of the two protamines used to package DNA in the sperm cell, 4) the role endocrines play in the histone to protamine transition and chromatin condensation, 5) the forces generated by protamine when it binds to DNA, and 6) the process of protamine removal from DNA when the sperm enters the oocyte.

The Kasinsky et al. review, which focuses on the evolution of the protamines, shows that the arginine-rich proteins that comprise the protamine family are likely to have evolved from the lysine-rich histone H1, through a general class of protamine-like proteins to the small, highly basic protamines found in mammalian sperm. One important outcome of this change to arginine-rich protamines, as suggested in this review, is that the evolution of the protein appears to have also led to a change in the pattern of chromatin organization within the nucleus and the development of a lamellar mediated process for generating a highly condensed form of chromatin. At the molecular level, the manner in which the protamines associate with the spermatid's DNA represents an excellent example of the biological self-assembly that is initiated when the protamine molecules, which are synthesized and pumped into the nucleus of the late-stage spermatid, binds to all but a small subset of the haploid genome. Upon binding, the protein neutralizes the negative charge on the phosphodiester backbone of both strands of DNA and functions as the ultimate repressor by shutting down the transcriptional activity of the entire spermatid genome. In addition to the physical compaction of the sperm genome, which contributes directly to the suppression of its genetic activity, the formation of the complex and its compaction also appears to protect the cell's DNA from physical damage and enables the packaging of a large volume of DNA into a small, more hydrodynamic and highly specialized cell nucleus - the sperm head.

Two different types of protamine have been isolated from mammalian sperm. Protamine P1, the smaller of the two proteins, is found bound to genomic DNA in the sperm of all mammals. Protamine P2, a slightly larger protein, is found in addition to protamine P1 in the sperm of primates, rodents and a selected subset of other species. As described in the Nanassy et al. review, alterations in the relative proportion of the P1 and P2 protamines in human sperm have a positive correlation with male infertility. While deficiencies of either P1 or P2 have been directly linked to infertility, the cause of the infertility may be related to an indirect effect such as altered histone retention or abnormally established epigenetic marks on developmental gene promoters in the sperm chromatin that ultimately lead to abnormal early embryo development and reduced pregnancy rates.....
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Document Type: Research Article

Publication date: 01 August 2011

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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