Anomalous Oligomerization Behavior of Aquaporin Z in Detergent and in Nanodiscs.

Aquaporins are tetrameric integral membrane proteins that act as water channels, and can also permeabilize membranes to other solutes. The monomer appears to be the functional form despite all aquaporins being organized as tetramers, which therefore must provide a clear functional advantage. In addition to this quaternary organization, some aquaporins can act as adhesion molecules in membrane junctions, when tetramers located in opposing membranes interact via their extracellular domains.

Mechanisms Underlying C-type Inactivation in Kv Channels: Lessons From Structures of Human Kv1.3 and Fly Shaker-IR Channels.

Voltage-gated potassium (Kv) channels modulate the function of electrically-excitable and non-excitable cells by using several types of "gates" to regulate ion flow through the channels. An important gating mechanism, C-type inactivation, limits ion flow by transitioning Kv channels into a non-conducting inactivated state. Here, we highlight two recent papers, one on the human Kv1.

Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.

We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.

A complex between the Zika virion and the Fab of a broadly cross-reactive neutralizing monoclonal antibody revealed by cryo-EM and single particle analysis at 4.1 Å resolution.

Zika virus (ZIKV) recently emerged as a major public health concern because it can cause fetal microcephaly and neurological disease such as the Guillain-Barré syndrome. A particularly potent class of broadly neutralizing antibodies (nAbs) targets a quaternary epitope located at the interface of two envelope proteins monomers, exposed at the surface of the mature virion. This "E-dimer-dependent epitope" (EDE), comprises the fusion loop of one monomer at the tip of domain II of E and a portion of the domains I and III of the adjacent monomer.

Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε.

The Mycobacterium tuberculosis (Mtb) FF-ATP synthase (α:β:γ:δ:ε:a:b:b':c) is an essential enzyme that supplies energy for both the aerobic growing and the hypoxic dormant stage of the mycobacterial life cycle. Employing the heterologous F-ATP synthase model system α:β:γ we showed previously, that transfer of the C-terminal domain (CTD) of Mtb subunit α (Mtα) to a standard F-ATP synthase α subunit suppresses ATPase activity. Here we determined the 3D reconstruction from electron micrographs of the α:β:γ complex reconstituted with the Mtb subunit ε (Mtε), which has been shown to crosstalk with the CTD of Mtα.

Structures of Mycobacterium smegmatis 70S ribosomes in complex with HPF, tmRNA, and P-tRNA.

Ribosomes are the dynamic protein synthesis machineries of the cell. They may exist in different functional states in the cell. Therefore, it is essential to have structural information on these different functional states of ribosomes to understand their mechanism of action.

Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope.

Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb_FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer.

Pseudologia fantastica: forensic and clinical treatment implications.

Pseudologia fantastica, also known as mythomania, or pathological lying, is a psychiatric phenomenon that is a mixture of fact and fiction involving fantasized events and self aggrandizing personal roles. It has been recognized in the field for over a century. In this case report we discuss three different cases, two of them presented in the acute inpatient setting and one outpatient setting.

SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster.

Background: The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.

The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins.

Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes.

SWI/SNF associates with nascent pre-mRNPs and regulates alternative pre-mRNA processing.

The SWI/SNF chromatin remodeling complexes regulate the transcription of many genes by remodeling nucleosomes at promoter regions. In Drosophila, SWI/SNF plays an important role in ecdysone-dependent transcription regulation. Studies in human cells suggest that Brahma (Brm), the ATPase subunit of SWI/SNF, regulates alternative pre-mRNA splicing by modulating transcription elongation rates.