Focus on proteins, surfaces, et al.

IN AN ARTICLE in The Scientist recently published, Marc Vidal, a geneticist at the Dana Farber Cancer Institute in Boston, reminds us that “. . .the proteome is vast. It’s like terra incognita,. . . we have a few settlers, we have to explore a huge amount of space. . .” (7a). There is astounding complexity to protein science, and we are just starting to comprehend the magnitude of the question. Amino acid chains, from small peptides to complex polymers, interacting with countless cellular and molecular components in the vertiginous waltz of metabolic pathways, each actor playing more than one part, entering and exiting yet again, mutating midways through the process and reappearing in a different configuration later on. . . . Thanks to the Human Genome Project, we now have all the elements for an astronomical number of new questions to ask, and we will need many scientific life spans to answer them. A couple of years back, many investigators and a certain number of curious laypeople answered the unusual appeal of a Stanford University project set out at www.foldingathome. stanford.edu: they installed protein folding calculations as screen saver programs on individual personal computers so that their cumulative activity could contribute to the titanic task of calculating protein secondary and tertiary structures. This creative tool has piqued the curiosity of many toward the exciting surprises of proteins and produced interesting data. However, we are barely scratching the, yes, pun intended, surface. About 30% of the proteins identified through the Human Genome Project are membrane-related proteins, and most of them contain one or more amphipathic peptides, configured as alpha-helical sequences, and closely dependent on the lipid system with which they associate (2). These findings suggest that a large body of information on all aspects of protein science, structure-function relationships, protein-lipid interactions, membrane protein sorting, protein folding, and a number of others will continue to come from interfacial studies (10, 12, 21). The use of proteins in surface chemistry appears a bit of a heresy to the classic lipid physicist for whom more than one component to the interface monolayer represents a contaminant. The biologist, however, has achieved endless entertainment from assessing the putative behavior of each amino acid chain in such systems. Proteins from a myriad of biological systems have been investigated through their surface activity using several different lipid moieties. Apolipoproteins (17), snake and bee venoms (4, 10), leader sequences (8), and viral envelope peptides (5) are among the proteins tested on surface monolayers to determine the molecular mechanisms by which an amino acid chain produces biological effects on intracellular processes via interactions with cell membranes. The results have been fascinating, somewhat distant from mainstream investigations, possibly appealing to the biophysicist more than to the biologist, and above all, far removed from the focus on molecular biology and therefore an avenue of renewed interest for the current season of protein studies. Few areas of the life sciences have contributed to the understanding of protein behavior at an interface as much as research on lung surfactant. Surfactant is part of the mammalian respiratory complex, a most unusual substance for composition and metabolic dynamics. Its synthesis, secretion, and reuptake have fascinated physiologists, biophysicists, and neonatologists since the relatively recent recognition of its existence (6, 18). A self-contained, exquisitely biophysical system comprising tightly regulated, vastly recycled, and unique components, such as proteins that behave like lipids and lipids enmeshed with water, surfactant has a crucial role in establishing and maintaining functional gas exchange units. Aggressive research and development in surfactant studies have rapidly produced successful contributions to the standards of care in neonatal medicine and a decrease in infant mortality, a pivotal index of social progress (1). The current neonatal fellows are amazed to discover that clinical surfactant was actually introduced only a dozen years ago. We are now perfectly comfortable with the choice of any of the various surfactants as a matter of personal preference, and only peripheral attention is paid to the basic science underAddress for reprint requests and other correspondence: R. Bruni, Dept. of Pediatrics, Div. of Neonatology, King/Drew Medical Center, Los Angeles, CA 90059 (E-mail: [email protected]). Am J Physiol Lung Cell Mol Physiol 283: L894–L896, 2002; 10.1152/ajplung.00137.2002.