Structural Insights into the Human Mitochondrial Pyruvate Carrier Complexes.

Pyruvate metabolism requires the mitochondrial pyruvate carrier (MPC) proteins to transport pyruvate from the intermembrane space through the inner mitochondrial membrane to the mitochondrial matrix. The lack of the atomic structures of MPC hampers the understanding of the functional states of MPC and molecular interactions with the substrate or inhibitor. Here, we develop the de novo models of human MPC complexes and characterize the conformational dynamics of the MPC heterodimer formed by MPC1 and MPC2 (MPC1/2) by computational simulations.

Extracellular gating of glucose transport through GLUT 1.

The ubiquitous glucose transporter 1 (GLUT1) is physiologically and pathologically relevant in energy metabolism of the CNS, skeletal muscles, cancer cells etc. Extensive experiments on GLUT1 produced thorough understandings of its expressions, functions, and structures which were recently resolved to atomic accuracy. However, theoretical understandings are still controversial about how GLUT1 facilitates glucose diffusion across the cell membrane.

The sterol regulatory element-binding protein 2 is dysregulated by tau alterations in Alzheimer disease.

Disturbed neuronal cholesterol homeostasis has been observed in Alzheimer disease (AD) and contributes to the pathogenesis of AD. As the master switch of cholesterol biosynthesis, the sterol regulatory element-binding protein 2 (SREBP-2) translocates to the nucleus after cleavage/activation, but its expression and activation have not been studied in AD which is the focus of the current study. We found both a significant decrease in the nuclear translocation of N-terminal SREBP-2 accompanied by a significant accumulation of C-terminal SREBP-2 in NFT-containing pyramidal neurons in AD.

Gibbs Free-Energy Gradient along the Path of Glucose Transport through Human Glucose Transporter 3.

Fourteen glucose transporters (GLUTs) play essential roles in human physiology by facilitating glucose diffusion across the cell membrane. Due to its central role in the energy metabolism of the central nervous system, GLUT3 has been thoroughly investigated. However, the Gibbs free-energy gradient (what drives the facilitated diffusion of glucose) has not been mapped out along the transport path.

Affinity and path of binding xylopyranose unto E. coli xylose permease.

Glucose transporters (GLUTs), expressed in all types of human cells, are responsible for the uptake of sugars as the primary energy source for the normal functions of good cells and for the abnormal growth of cancer cells. The E. coli xylose permease (XylE), a homologue of human GLUTs, has been investigated more thoroughly than other major facilitator proteins in the current literature.