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The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis. [ABSTRACT FROM AUTHOR]

The microtubule (MT) and actin cytoskeletons drive many essential cellular processes, yet fairly little is known about how their functions are coordinated. One factor that mediates important cross talk between these two systems is WHAMM, a Golgi-associated protein that utilizes MT binding and actin nucleation activities to promote membrane tubulation during intracellular transport. Using cryoelectron microscopy and other biophysical and biochemical approaches, we unveil the underlying mechanisms for how these activities are coordinated. We find that WHAMM bound to the outer surface of MT protofilaments via a novel interaction between its central coiled-coil region and tubulin heterodimers. Upon the assembly of WHAMM onto MTs, its N-terminal membrane-binding domain was exposed at the MT periphery, where it can recruit vesicles and remodel them into tubular structures. In contrast, MT binding masked the C-terminal portion of WHAMM and prevented it from promoting actin nucleation. These results give rise to a model whereby distinct MT-bound and actin-nucleating populations of WHAMM collaborate during membrane tubulation. [ABSTRACT FROM AUTHOR]

Neurotransmitters are released through nascent fusion pores, which ordinarily dilate after bilayer fusion, preventing consistent biochemical studies. We used lipid bilayer nanodiscs as fusion partners; their rigid protein framework prevents dilation and reveals properties of the fusion pore induced by SNARE (soluble N-ethylmaleimide--sensitive factor attachment protein receptor). We found that although only one SNARE per nanodisc is required for maximum rates of bilayer fusion, efficient release of content on the physiologically relevant time scale of synaptic transmission apparently requires three or more SNARE complexes (SNAREpins) and the native transmembrane domain of vesicle-associated membrane protein 2 (VAMP2). We suggest that several SNAREpins simultaneously zippering their SNARE transmembrane helices within the freshly fused bilayers provide a radial force that prevents the nascent pore from resealing during synchronous neurotransmitter release. [ABSTRACT FROM AUTHOR]

The combination of classical Hodgkin's lymphoma (cHL) and non-Hodgkin lymphoma coexisting in the same patient is not common, especially in one extranodal location. Here we present a rare case of composite diffuse large B-cell lymphoma (DLBCL) and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain. Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining. Epstein-Barr virus (EBV) infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1. Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulin κ light chain gene rearrangements. The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP (RCHOP) chemotherapy regimen. This case report showed that the two distinct components, DLBCL and cHL, appeared to originate from the same clonal progenitor cell, and that EBV infection was not essential for transformation during the course of tumorigenesis.