Protein Folding: Past and Future
Fifty years ago the Nobel Prize in chemistry was awarded to Max Perutz and John Kendrew for determining the structure of globular proteins. Since first viewing their structure of myoglobin, scientists have sought to understand protein folding. Dill and MacCallum (p. 1042) review the progress that has been made on three central questions: What is the code that relates sequence to structure? How do proteins fold so fast? Can protein structure be computationally predicted? While we have come some way toward answering these questions, new questions have been gene rated. It is no longer useful to talk about “solving the protein-folding problem”—protein folding has grown into a field of research where the next 50 years promise to be as exciting as the last.
Forming the Moon from Earth
It is thought that the Moon formed after a Mars-sized planet hit Earth about 4.5 billion years ago. Computer simulations of this event predict that the Moon was produced primarily from material from the impacting planet. However, the Moon has a similar composition to that of Earth, and the impacting planet would likely have had a different composition. Prior models assumed that the impact left the Earth-Moon system with the same angular momentum as it has today (see the Perspective by Halliday). Ćuk and Stewart (p. 1047, published online 17 October; see the cover) show that the angular momentum of the Earth-Moon system could have decreased by half after the Moon-forming impact, opening the door to new impact models. For example, simulations suggest that high-velocity impacts onto a fast-spinning early Earth can lead to a Moon formed primarily from Earth's mantle. Canup (p. 1052, published online 17 October) considered instead lower-velocity impacts by planets comparable in mass to the proto-Earth, which could generate a Moon and an Earth with similar compositions.
Watching a Breakdown
One of the key challenges in scaling up biofuels manufacturing is development of a cost-effective way to break down cellulose into sugars for subsequent fermentation. Ding et al. (p. 1055) applied several different types of microscopy to understand the details of how cellulase enzymes perform this task, in the interest of ultimately optimizing the procedure. After lignin removal, fungal cellulases penetrated the remaining cellulose pore structure more efficiently than did bacteria-derived multienzyme complexes. However, this behavior hinges on a lignin extraction scheme that preserves the native architecture of the cellulose.
When Molecules Collide
As advances in computing power and algorithm design parallel the increasing sophistication of experimental apparatus, theory and measurement are perpetually trading places as to which can detail the dynamics of molecular interactions more precisely. At present, collisions of an atom with a diatomic molecule can be studied comparably in both domains. In contrast, collisions of two diatomics each bearing an unpaired electron manifest too many degrees of freedom for computational quantum mechanics. Kirste et al. (p. 1060) have now experimentally resolved the rotational dynamics of one such case—the inelastic scattering of NO + OH—and find that a simplified theoretical model focusing on long range interactions predicts the outcome surprisingly well. Such approximations could render many analogous systems moderately predictable.
Fathoming Publication Strategies
While many studies have tracked numbers of citations after publication, such studies cannot reveal how prepublication dynamics affects subsequent citation history. Calcagno et al. (p. 1065, published online 11 October) surveyed the submission history of more than 80,000 articles published in 16 fields of biology in 2006–2008 and constructed a social network based on manuscript flows among scientific journals. High-impact journals occupied central positions in the network. A majority of manuscripts were published in the first journal to which they were submitted. However, submission history affected the post-publication impact (citation count) of articles, with manuscripts requiring resubmission eventually receiving more citations.
Exploiting Seismic Noise
Typically, seismic imaging has been based on examining the seismic waves that traveled from a known source, usually an earthquake, to a seismograph. Poli et al. (p. 1063; see the Perspective by Prieto) now show that correlations of body waves in seismic noise can yield information about Earth's deep interior. An array in Finland, supplemented by other stations, was used to examine reflections from two major seismic boundaries within Earth's mantle at depths of about 410 and 660 km thought to be associated with mineralogical changes in Earth's interior. The data imply that the upper discontinuity extends over about 15 kilometers whereas the deeper one is only about 4 km thick.
When intracellular pathogens like Legionella pneumophila take up residence in mammalian host cells, they must combat the efforts of the host cell to attack them. Autophagy is a process by which cells digest their own constituents, often involved in response to starvation or pathogen attack. Choy et al. (p. 1072, published online 25 October) now describe how L. pneumophila can inhibit the autophagy pathway in eukaryotic cells, and provide a detailed description of the biochemical mechanism. A Legionella effector protein, RavZ, acts as a very potent enzyme that specifically deconjugates a key autophagy protein, Atg8, from autophagosomal membranes, thus blocking autophagy.
Getting the Feel of DNA
To transcribe a gene, RNA polymerase (RNAP) must unwind the promoter DNA to form a “transcription bubble” and the RNAP-promoter open complex (RPo). The activity of RPo is critical for the regulation of gene expression. Zhang et al. (p. 1076, published online 18 October) describe crystal structures of bacterial RPo, together with the transcription initiation factor σ, from Thermus thermophilus, variously in complex with promoter DNA and an RNA primer. RNAP and σ recognize the promoter through sequence-specific contacts with transcription-bubble, nontemplate-strand DNA. Critical interactions occur through the unstacking of DNA bases and their insertion into pockets on the surfaces of the two proteins, allowing direct sensing of the DNA sequence.
Cancer Stem Cells: A Moving Target?
Glioblastoma multiforme (GBM) is a highly aggressive human brain tumor. The prevailing “cancer stem cell hypothesis” posits that GBMs arise primarily from neuronal stem cells. Now, Friedmann-Morvinski et al. (p. 1080, published online 18 October; see the Perspective by Krivtsov and Armstrong) suggest that this hypothesis may be too restrictive. In mouse models, brain tumors resembling human GBMs could form from fully differentiated cells such as astrocytes and neurons. Upon acquiring certain genetic alterations, mature brain cells may thus be capable of dedifferentiating into a progenitor-like cell, which could then initiate and maintain tumor growth.
Local Optima for Plankton
Recent ocean warming has changed the seasonality and composition of the marine phytoplankton. Thomas et al. (p. 1085, published online 25 October) investigated the direct effect of temperature on phytoplankton. By fitting published data to reaction temperature norms for 194 phytoplankton strains isolated from a wide latitudinal range, the resultant temperature-related traits (maximum growth rate, temperature optimum, and thermal niche width) reveal latitudinal trends in temperature optima and diversity. Biogeographical differences indicate an increased susceptibility of tropical strains to further warming, and modeling predicts poleward shifts of tropical strains and a loss of phytoplankton diversity in the tropics within the next hundred years.
Double Delivery During Plant Fertilization
Double fertilization is a defining feature of flowering plants and involves two nonmotile male gametes (sperm cells) and two female gametes (egg cell and central cell). Both fertilization events are necessary for reproductive success. It is not clear how flowering plants ensure the reliable and on-time fusion of the two pairs of gametes, while preventing polyspermy. Sprunck et al. (p. 1093; see the Perspective by Snell) now show that gamete interactions in Arabidopsis depend on small cysteine-rich EGG CELL 1 (EC1) proteins that accumulate in storage vesicles of the egg cell and that are released during sperm-egg interaction. EC1 peptides trigger the delivery of a fusogen to the sperm cell surface. An intercellular link connects the two sperm cells throughout the gamete fusion process and could play a role in preventing the spontaneous fusion of activated sperm cells.
Synchronous Brain Activity
Synchronization of neuronal activity across different brain areas varies according to working memory load or the locus of attention. It is thought that synchronization serves as a general mechanism for increasing effective cross-area communication during memory and attention tasks. However, it is not known if synchronization carries specific content. Salazar et al. (p. 1097, published online 1 November) recorded from multiple electrodes across parietal and prefrontal cortices of monkeys and found content-specific synchronization for both location and object identity in a working memory task. The findings suggest that the contents of working memory could be maintained through site-specific synchrony across brain areas.
Help for Starving Cells
As tumors grow larger, individual tumor cells respond to the dwindling supply of nutrients by changing the way they produce energy. The enzyme pyruvate kinase isoform M2 (PKM2) is an important component of this “metabolic reprogramming.” In a study aimed at identifying how PKM2 is regulated, Keller et al. (p. 1069, published online 18 October) found that a cellular metabolite called SAICAR (succinylaminodazolecarboxamide ribose-5′-phosphate) stimulates PKM2 activity and promotes cancer cell survival when glucose is limited. SAICAR is an intermediate in the pathway for de novo biosynthesis of nucleotides and its interaction with PKM2 may help cells coordinate their mode of energy generation with nutrient conditions.
Dissecting HCMV Gene Expression
Most of us are infected with human cytomegalovirus (HCMV), but severe disease is almost always limited to immunocompromised individuals or newborn infants. The virus has a relatively large (∼240 kb) DNA genome and shows a complex pattern of gene transcription, hinting at a complex regulatory and coding capacity. Stern-Ginossar et al. (p. 1088) mapped ribosome positions on HCMV transcripts during the course of viral infection of human fibroblast cells. The data suggest the presence of novel open reading frames (ORFs) lying within existing ORFs; very short ORFs upstream of canonical ORFs; ORFs antisense to canonical ORFs; and short, conserved ORFs encoded by long RNAs. Select ORFs were translated, dramatically expanding the coding capacity of the HCMV genome.