Ken Biegeleisen | PubMed Health

PubMed2006

The probable structure of the protamine-DNA complex.

A detailed molecular structure is proposed for the human protamine-DNA complex, which has hitherto been largely a mystery. The structure was created with virtual modeling software (AmiraMol), employing logical deduction as the primary investigative tool. A beta-sheet structure for the protein component is essentially mandated, as the alternatives can be decisively excluded. A dimeric structure too is essentially mandated, since the cysteine residues of protamines P1 and P2 are invariably aligned in all species having both chains. The cross-sectional and axial spacings of arginine guanidinium groups in this protein structure can be perfectly aligned with those of phosphate groups in DNA according to the DNA structure proposed by Wu. This is a non-helical structure, whose possible occurrence in certain plasmids has been suggested by experimental observations. The unit cell of this protamine-DNA complex is essentially devoid of steric hindrances, and heavily favored by a multitude of ionic and hydrogen bonds. The packing of adjacent "unit cells" of the protamine-DNA structure is based on a complex array of salt bridges, the mere existence of which is so fortuitous that it is virtually inconceivable that it comes about through a mere modeling "coincidence". The possible significance of the structure beyond the sperm cell is discussed.

Amino Acid Sequence↗

PubMed2002

Topologically non-linked circular duplex DNA.

The discovery of circular DNA, over 30 years ago, introduced an element of uneasiness in what had been, up to that point, the almost picture-perfect story of the elucidation of the molecular biology of heredity. If DNA indeed has the Watson-Crick right-handed helical secondary structure, then in circular DNA, thousands, or perhaps even millions of twists must be removed in each generation, and re-wound in the next generation. Although enzyme systems adequate for this task have long since been found and characterized, there have nevertheless arisen a number of proposals for alternative DNA structures in which the strands are topologically non-linked, so that they might separate during replication without having to be unwound. These structures have generally been put forth as theory only, and have been largely unaccompanied by experimental evidence to support their applicability to native DNA from living systems. Recently, however, a report has emerged suggesting that it might be possible to separate, intact, the individual single-stranded circular half-chromosomes which constitute the double-stranded circular chromosomes of certain plasmids. This would not be possible unless the chromosomes had one of the alternative, topologically non-linked structures. It is widely believed that after a half-century of worldwide DNA research, any significant change to the Watson-Crick structure is unlikely to stand up to scrutiny. Nevertheless, the present author has found that in many instances in which the behavior of circular duplex DNA is considered to be explicable only in terms of the topologically linked helical model, it is also possible to explain that same behavior in terms of a topologically non-linked model. It is necessary, in these instances, to make certain logical assumptions which cannot be conclusively proven at the present time. The author herein offers an example of one such instance, namely an examination of the behavior of circular duplex DNA in an alkaline titration experiment, where conformational changes in DNA are deduced from changes in its buoyant density at pH's between 7 and 14. These data have been explained in terms of topological linkage between the DNA strands, but they can also be explained without invoking any such topological linkage, provided that the above-mentioned logical assumptions can be accepted. The principles which emerge from this are applicable to other settings in which knowledge of the topology of DNA is critical to the understanding of observed phenomena.

DNA, Circular↗