Protein folding and unfolding are coupled to a range of biological phenomena, from the regulation of cellular activity to the onset of neurodegenerative diseases. Defining the nature of the conformations sampled in nonnative proteins is crucial for understanding the origins of such phenomena. We have used a combination of nuclear magnetic resonance (NMR) spectroscopy and site-directed mutagenesis to study unfolded states of the protein lysozyme. Extensive clusters of hydrophobic structure exist within the wild-type protein even under strongly denaturing conditions. These clusters involve distinct regions of the sequence but are all disrupted by a single point mutation that replaced residue Trp ⁶² with Gly located at the interface of the two major structural domains in the native state. Thus, nativelike structure in the denatured protein is stabilized by the involvement of Trp ⁶² in nonnative and long-range interactions.

Energy conversion in complex 1: ATP, the energy source of the cell, is synthesized by a protein residing in the mitochondrial inner membrane. The synthesis is driven by a proton gradient generated by redox reactions that transfer electrons between a series of enzymes in the membrane. The largest complex in this electron transfer chain is the 1-MD complex 1. It couples electron transfer from NADH to ubiquinone to the translocation of four protons. Zickermann et al. report the crystal structure of a complex comprising the 14 central subunits and the largest accessory subunit of mitochondrial complex 1 from a yeast-genetic model at 3.6 Å resolution. The structure identifies four potential proton translocation pathways and gives insight into how energy from the redox reactions is transmitted to drive proton pumping. Science , this issue p. 44