The inner membranes of mitochondria contain three multi-subunit enzyme complexes that act successively to transfer electrons from NADH to oxygen, which is reduced to water (Fig. I). The first enzyme in the electron transfer chain, NADH:ubiquinone oxidoreductase (or complex I), is the subject of this review. It removes electrons from NADH and passes them via a series of enzyme-bound redox centres (FMN and Fe-S clusters) to the electron acceptor ubiquinone. For each pair of electrons transferred from NADH to ubiquinone it is usually considered that four protons are removed from the matrix (see section 4.1 for further discussion of this point).

Electrophoresis of DNA through gels of agarose or polyacrylamide (PA) has been one of the most widely used techniques of molecular biology during the past decade, serving both analytical and preparative purposes. The molecular theory of this process has been developing slowly over the same period of time as the result of the efforts of a small but expanding group of people. Initially simple, the theory has grown in ways that no one anticipated at the beginning, partly in response to unexpected experimental discoveries. In this review we describe its current state, including both solved and unsolved problems.

In spite of several great breakthroughs, the overall rate of progress in determining high-resolution structures of membrane proteins has been slow. This is entirely due to the scarcity of suitable, well-ordered crystals. Most membrane proteins are multimeric complexes with a composite molecular mass in excess of 50000 Da which puts them outside the range of current solution NMR techniques. For the foreseeable future, detailed information about the structure of large membrane proteins will therefore depend on crystallographic methods.

This review will consider solution studies of structure and interactions of DNA and DNA complexes using linear dichroism spectroscopy, with emphasis on the technique of orientation by flow. The theoretical and experimental background to be given may serve, in addition, as a general introduction into the state of the art of linear dichroism spectroscopy, particularly as it is applied to biophysical problems.

Ion transport by peptide channels has been the major theme in the work of the late P. Läuger. His theoretical and experimental approaches provided the basis for a deeper understanding of pore-mediated ion permeation through biological membranes. This review on a ligand–gated ion channel protein from the mammalian brain is dedicated to the memory of this outstanding scientist.

Following the first determinations of protein structures in the late 1950s and the early 1960s (see for example Kendrew et al. 1960; Perutz, 1964), the three-dimensional structures of several hundred proteins have been elucidated by X-ray diffraction on single crystals. By the end of 1991, approximately 150 entries of proteins with substantially different sequences and a well resolved structure (Hobohm et al. 1992) were deposited in the Protein Data Bank (Bernstein et al. 1977; Abola et al. 1987). In addition, many structures of homologous proteins or of mutants have been described, bringing the total number of entries to about 600. While it was soon accepted that almost all of these structures do indeed give a correct picture of the fold of the active protein in spite of the non-physiological environment of single crystals, it is not clear to what extent structural details are reliably described by these structures. In particular the surface of a protein may be modified due to the dense packing of protein molecules in the crystal lattice. A detailed knowledge of the protein surface is, however, essential for the understanding of the function of the protein.

The fundamental relationship between structure and function has served to guide investigations into the workings of living systems at all levels - from the whole organism to individual cells on down to individual molecules. When X-ray crystallography began to reveal the three-dimensional structures of proteins like myoglobin, lysozyme and RNase A, protein chemists were well prepared to draw inferences about functional mechanisms from the precise positioning of amino acid residues they could see. The close proximity between an amino acid side chain and a chemical group on a bound ligand strongly suggests a functional role for that side chain in binding affinity and specificity. Likewise, the nearly universal finding of large clusters of hydrophobic side chains buried in the core of proteins strongly supports a major functional role of hydrophobic interactions in protein folding and stability. Even though eminently plausible hypotheses like these, grounded in the most fundamental principles of chemistry and the logic of structure–function relationships, become widely accepted and make their way into textbooks, protein chemists have felt compelled to search for ways to test them and put them on a more quantitative basis.

The scientific community will remember Peter Läuger as an exceptional man combining a generous personality and a sharp and skilful mind. He was able to attract by his views the interest of a large spectrum of biologists concerned by the mechanism of ion translocation through membranes. Yet, he was not a man with a single technique or theory. Using an authentically multidisciplinary approach, his ambition was to ‘understand transmembrane transport at the microscopic level, to capture its dynamics in the course of defined physiological processes’ (1987). According to him, ‘new concepts in the molecular physics of proteins’ had to be imagined, and ‘the traditional static picture of proteins has been replaced by the notions that proteins represent dynamic structures, subjected to conformational fluctuations covering a very wide time-range’ (1987).

The elucidation of the molecular mechanisms whereby ions and polar molecules are translocated across the hydrophobic barrier of a lipid bilayer in biological membranes is one of the most challenging problems in biological research. Specific membrane proteins, such as pumps, carriers and channels, play the central role in the various translocation pathways. Recent progress in expression cloning has provided the sequence of a number of biologically important membrane proteins and in principle the door is open to investigate every protein which might be of importance in the central signal transduction and transport processes. Unfortunately, to date there are only a few examples where the three-dimensional structure of membrane proteins are known at atomic resolution. The photosynthetic reaction centres from purple bacteria (Deisenhofer et al. 1985), bacteriorhodopsin (Henderson et al. 1990) and the large porin channel of Rhodobacter capsulata (Weiss et al. 1991). According to these structural data membrane proteins seem to fold in general in membrane-spanning α-helices and β-strands in order to saturate hydrogen bonds. Only these two motifs seem to form stable structures which can be in contact with the hydrophobic lipid interior of a membrane.

The advent of methods for forming and studying lipid bilayer membranes (Mueller et al. 1962; Hanai et al. 1964) opened the way for some fifteen years of intensive and productive study of the properties of lipid soluble ions and ion carriers. I expect that none will dissent from the view that Peter Läuger and his associates, including R. Benz and G. Stark, did more than any other research group to advance the study of the mechanism of the charge transfer. Between 1970 and 1981 they published more than 25 substantial contributions. Thus it is appropriate that this memorial issue should contain a short review of this subject. As I have the highest regard for their work I was very pleased to be asked to write such a chapter. There is little point in providing another general survey because Läuger's group published reviews at the end of this period (Benz et al. 1980; Läuger et al. 1981) and I also reviewed the field at length (Hladky, 1979a). Instead I would like to consider the three cornerstone papers of 1971, some of the difficulties that arose from those papers, how they were overcome, and three aspects of the description that are still incomplete.

Peter Läuger introduced me (P.C.J.) to the field of ion-channel electrostatics while I was a sabbatical visitor at Konstanz in 1978–79. Läuger pointed out that the relative conductance of hydrophobic ions through phosphatidyl choline (PC) and glyceryl monooleate (GMO) membranes differed by a factor of about 100 (Hladky & Haydon, 1973), quite consistent with the difference in the water-membrane potential differences in the two systems (Pickar & Benz, 1978). However, cation conductance through gramicidin channels spanning these membranes only differs by a factor of 2–3 (Bamberg et al. 1976). Why? It is the pursuit of an answer to this question which led me into my researches in this field.