Helix-capping motifs are specific patterns of hydrogen bonding and hydrophobic interactions found at or near the ends of helices in both proteins and peptides. In an a-helix, the first four >N-H groups and last four >C=O groups necessarily lack intrahelical hydrogen bonds. Instead, such groups are often capped by alternative hydrogen bond partners. This review enlarges our earlier hypothesis (Presta LG, Rose GD. 1988. Helix signals in proteins. Science 240:1632-1641) to include hydrophobic capping. A hydrophobic interaction that straddles the helix terminus is always associated with hydrogen-bonded capping. From a global survey among proteins of known structure, seven distinct capping motifs are identified-three at the helix N-terminus and four at the C-terminus. The consensus sequence patterns of these seven motifs, together with results from simple molecular modeling, are used to formulate useful rules of thumb for helix termination. Finally, we examine the role of helix capping as a bridge linking the conformation of secondary structure to supersecondary structure.Keywords: alpha helix; protein folding; protein secondary structure The a-helix is characterized by consecutive, main-chain, i + i -4 hydrogen bonds between each amide hydrogen and a carbonyl oxygen from the adjacent helical turn (Pauling & Corey, 1951). This pattern (Fig. 1) is interrupted at helix termini because, upon termination, no turn of helix follows to provide additional hydrogen bond partners. Such end effects are substantial, encompassing two-thirds of the residues for the protein helix of average length (Presta & Rose, 1988). Further, helix geometry hinders solvent access to amide groups in the first turn of the helix, inhibiting interaction with water and necessitating alternative hydrogen bonds. The term helix "capping" (Richardson & Richardson, 1988a) has been used to describe such alternative hydrogen bond patterns that can satisfy backbone >N -H and >C = 0 groups in the initial and final turns of the helix (Presta & Rose, 1988).Many studies involving helix capping have been conducted since publication of our initial hypothesis nine years ago (Presta & Rose, 1988). As we had proposed, amide hydrogens at the helix N-terminus are indeed satisfied predominantly by side-chain H-bond acceptors. In contrast, carbonyl oxygens at the C-terminus are satisfied primarily by backbone >N -H groups from the turn following the helix. Further, these hydrogen-bonding patterns at either helix end are accompanied by a companion hydrophobic interaction between apolar residues in the a-helix and its flanking turn. This hydrophobic component of helix capping was unanticipated.The main purpose of this review is to enlarge our previous definition of helix capping and to document the common capping motifs. Qpically, protein helices terminate in a hydrophobic interaction that straddles the helix termini (i.e., an interaction between two hydrophobic residues close in sequence, one within the helix, the other external to the helix). In this interaction,...

No abstract

A predictive rule for protein folding is presented that involves two recurrent glycine-based motifs that cap the carboxyl termini of alpha helices. In proteins, helices that terminated in glycine residues were found predominantly in one of these two motifs. These glycine structures had a characteristic pattern of polar and apolar residues. Visual inspection of known helical sequences was sufficient to distinguish the two motifs from each other and from internal glycines that fail to terminate helices. These glycine motifs--in which the local sequence selects between available structures--represent an example of a stereochemical rule for protein folding.

Cyanobacteria are photosynthetic organisms and are the only prokaryotes known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 produce oxygen and can also fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. To accommodate such antagonistic processes, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of the two processes: photosynthesis during the day and nitrogen fixation at night. Although previous studies have examined periodic changes in transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5,000 genes in Cyanothece 51142 during two consecutive diurnal periods. Our analysis showed that Ϸ30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece 51142. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes encoding enzymes in numerous individual biochemical pathways, such as glycolysis, oxidative pentose phosphate pathway, and glycogen metabolism, were coregulated and maximally expressed at distinct phases during the diurnal cycle. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium.circadian ͉ cyanobacteria ͉ microarray ͉ nitrogen fixation ͉ photosynthesis M any organisms, including animals, plants, fungi, and algae, have evolved an internal timing system to anticipate daily variations in their environment. Circadian behavior, the endogenous oscillation of processes with a period length of Ϸ1 day, is a fundamental aspect of biology that allows organisms to respond to their environment. The circadian clock controls a wide variety of biological activities, including sleep-wake cycles in mammals, leaf movements of plants, conidiation of Neurospora, and bioluminescence in dinoflagellates (1-4). In contrast, prokaryotes were long thought incapable of daily biological rhythms, because their generation times are typically shorter than a circadian period (5). During the past 15 years, numerous studies have shown that cyanobacteria, photosynthetic microbes, are the only prokaryotes known to have a circadian clock (6, 7). Although components of the circadian clock have been identified and analyzed in detail in cyanobacteria (8-10), the interactions between the clock and cellular physiology and metabolism have not been well elucidated.In cyanobacteria, oxygenic photosynthesis is a central metabolic process. In ad...

These findings support the theory that in some cases CRS results from an immune hyperresponsiveness to commensal organisms.