FSH, a glycoprotein hormone, and the FSH receptor (FSHR), a G protein-coupled receptor, play central roles in human reproduction. We report the crystal structure of FSH in complex with the entire extracellular domain of FSHR (FSHR ED ), including the enigmatic hinge region that is responsible for signal specificity. Surprisingly, the hinge region does not form a separate structural unit as widely anticipated but is part of the integral structure of FSHR ED . In addition to the known hormone-binding site, FSHR ED provides interaction sites with the hormone: a sulfotyrosine (sTyr) site in the hinge region consistent with previous studies and a potential exosite resulting from putative receptor trimerization. Our structure, in comparison to others, suggests FSHR interacts with its ligand in two steps: ligand recruitment followed by sTyr recognition. FSH first binds to the high-affinity hormone-binding subdomain of FSHR and reshapes the ligand conformation to form a sTyr-binding pocket. FSHR then inserts its sTyr (i.e., sulfated Tyr335) into the FSH nascent pocket, eventually leading to receptor activation.F SH is a gonadotropin that stimulates steroidogenesis and gametogenesis in the gonads. Secreted by the anterior pituitary gland, FSH regulates the menstrual cycle and ovarian follicular maturation in women and supports sperm production in men. FSH acts by binding to the FSH receptor (FSHR) on the granulosa cell surface in ovaries and the Sertoli cell surface in testes. The stimulated receptor leads to the dissociation of α-and βγ-subunits of G protein heterotrimer inside the cell. The α-subunit activates adenylyl cyclase, resulting in an increase of cAMP levels, and ultimately leads to the increased steroid production that is necessary for follicular growth and ovulation in women. The free βγ dimers recruit G protein-coupled receptor (GPCR) kinases to the receptor, which, in turn, lead to the recruitment of β-arrestin to the receptor (1). FSH is used clinically for controlled ovarian stimulation in women treated with assisted reproductive technologies and also for the treatment of anovulatory infertility in women and hypogonadotropic hypogonadism in men. The central role of FSH in human reproduction makes its receptor a unique pharmaceutical target in the field of fertility regulation (2-4).The glycoprotein hormone (GPH) family has four members: FSH; two other pituitary hormones, luteinizing hormone and thyroid-stimulating hormone (TSH); and one placental hormone, chorionic gonadotropin. The four members are homologous in sequence, structure, and function. Each member is a heterodimer composed of a common α-subunit and a hormone-specific β-subunit. The crystal structures of FSH and human CG (hCG) revealed that both α-and β-subunits adopt similar folds of cystineknot architecture (5-7). The assembled α-and β-heterodimers bind to their respective receptors with high affinity and hormone specificity, resulting in similar signaling pathways but distinct biological responses.

With the lateral coplanar heterojunctions of two-dimensional monolayer materials turning into reality, the quantitative understanding of their electronic, electrostatic, doping, and scaling properties becomes imperative. In contrast to traditional bulk 3D junctions where carrier equilibrium is reached through local charge redistribution, a highly nonlocalized charge transfer (trailing off as 1/x away from the interface) is present in lateral 2D junctions, increasing the junction size considerably. The depletion width scales as p(-1), while the differential capacitance varies very little with the doping level p. The properties of lateral 2D junctions are further quantified through numerical analysis of realistic materials, with graphene, MoS2, and their hybrid serving as examples. Careful analysis of the built-in potential profile shows strong reduction of Fermi level pinning, suggesting better control of the barrier in 2D metal-semiconductor junctions.

Traditional inductors in modern electronics consume excessive areas in the integrated circuits. Carbon nanostructures can offer efficient alternatives if the recognized high electrical conductivity of graphene can be properly organized in space to yield a current-generated magnetic field that is both strong and confined. Here we report on an extraordinary inductor nanostructure naturally occurring as a screw dislocation in graphitic carbons. Its elegant helicoid topology, resembling a Riemann surface, ensures full covalent connectivity of all graphene layers, joined in a single layer wound around the dislocation line. If voltage is applied, electrical currents flow helically and thus give rise to a very large (∼1 T at normal operational voltage) magnetic field and bring about superior (per mass or volume) inductance, both owing to unique winding density. Such a solenoid of small diameter behaves as a quantum conductor whose current distribution between the core and exterior varies with applied voltage, resulting in nonlinear inductance.

Background: A carbohydrate of follicle-stimulating hormone (FSH) has been proposed to sterically block other FSH molecules from binding to the putative receptor (FSHR) trimer.Results: FSH increases its receptor binding by 3-fold when the steric hindrance is removed.Conclusion: FSHR forms a functional trimer.Significance: This knowledge may improve designs of therapeutic drugs targeting FSHR.

Two-dimensional (2D) crystal growth over substrate features is fundamentally guided by the Gauss-Bonnet theorem, which mandates that rigid, planar crystals cannot conform to surfaces with nonzero Gaussian curvature. Here, we reveal how topographic curvature of lithographically designed substrate features govern the strain and growth dynamics of triangular WS2 monolayer single crystals. Single crystals grow conformally without strain over deep trenches and other features with zero Gaussian curvature; however, features with nonzero Gaussian curvature can easily impart sufficient strain to initiate grain boundaries and fractured growth in different directions. Within a strain-tolerant regime, however, triangular single crystals can accommodate considerable (<1.1%) localized strain exerted by surface features that shift the bandgap up to 150 meV. Within this regime, the crystal growth accelerates in specific directions, which we describe using a growth model. These results present a previously unexplored strategy to strain-engineer the growth directions and optoelectronic properties of 2D crystals.

The growth of graphene on copper foil has attracted attention in the last two years due to its feasibility for a controllable growth process. One of the key issues remaining for practical application of graphene in solid-state devices is growth with a large grain size. Because the C–C bond in graphene is strong enough to prevent the evaporation–condensation process, Smoluchowski ripening is expected to be the dominant process for coalescence. In this article, we present the initial growth process of graphene on a Cu foil via the chemical vapor deposition method by using secondary electron microscopy and Raman microscopy. In contrast to the other transition-metal substrates, such as Ir and Rh, the center of graphene islands binds to the substrate more rigidly than the edge. For the growth with a large grain size, the graphene should be grown on a substrate with a low diffusion barrier for the carbon clusters (or islands) with low flux; this is the controlling parameter for the grain size. In addition, high-temperature growth (or annealing) generally becomes a dominant condition for the completion of graphene growth with large grains after the coalescence.

Moreover, analyses of Src؊/؊ , Yes ؊/؊ , and Fyn ؊/؊ fibroblasts showed that Src expression was inhibitory to TNF␣-stimulated IL-6 production. These studies provide evidence for a novel Srcindependent FAK to MAPK signaling pathway regulating IL-6 expression with potential importance to inflammation and tumor progression. Focal adhesion kinase (FAK)2 is best known for its role as an integrin-stimulated protein-tyrosine kinase (1). FAK is recruited to sites of integrin clustering via interactions of its C-terminal domain with integrin-associated proteins such as talin and paxillin. FAK contains a central kinase domain, C-terminal proline-rich regions that serve as binding sites for Src homology 3 (SH3) domain-containing proteins, and an N-terminal band 4.1, ezrin, radixin, moesin homology (FERM) domain that acts to regulate FAK kinase activity through an auto-inhibitory mechanism (2, 3). Integrin clustering promotes FAK activation, results in FAK phosphorylation at Tyr-397 (Tyr(P)-397), promotes Src family protein-tyrosine kinase binding to the FAK Tyr(P)-397 site, and facilitates the formation of the FAK-Src signaling complex that results in the secondary phosphorylation of FAK at Tyr-861 and Tyr-925 (4, 5).

A high‐yield one‐pot synthesis of S‐linked glycosyl amino acids 1 has been developed (see scheme; DMF=dimethyl formamide) and used in the solid‐phase synthesis of S‐linked glycopeptides. This approach has been shown to be efficient for the synthesis of various S‐linked glycosyl amino acid building blocks.