Ju Mei,†,‡,∥ Nelson L. C. Leung,†,‡,∥ Ryan T. K. Kwok,†,‡ Jacky W. Y. Lam,†,‡ and Ben Zhong Tang*,†,‡,§ †HKUST-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China ‡Department of Chemistry, HKUST Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Biomedical Engineering, State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

Aggregation-Induced Emission: Together We Shine, United We Soar!

MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis of any steric problems within the molecules as well as updated dihedral-angle diagnostics, and it can calculate and display the H-bond and van der Waals contacts in the interfaces between components. An integral step in the process is the addition and full optimization of all hydrogen atoms, both polar and nonpolar. New analysis functions have been added for RNA, for interfaces, and for NMR ensembles. Additionally, both the web site and major component programs have been rewritten to improve speed, convenience, clarity and integration with other resources. MolProbity results are reported in multiple forms: as overall numeric scores, as lists or charts of local problems, as downloadable PDB and graphics files, and most notably as informative, manipulable 3D kinemage graphics shown online in the KiNG viewer. This service is available free to all users at http://molprobity.biochem.duke.edu.

http://kinemage.biochem.duke.edu/teaching/workshop/MolProbity/pdfs/2007DavisNAR35.pdf

MolProbity: all-atom contacts and structure validation for proteins and nucleic acids

Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.

Molecular mechanisms of antibiotic resistance.

The bacteria cell envelope is a complex multilayered structure that serves to protect these organisms from their unpredictable and often hostile environment. The cell envelopes of most bacteria fall into one of two major groups. Gram-negative bacteria are surrounded by a thin peptidoglycan cell wall, which itself is surrounded byan outer membrane containing lipopolysaccharide. Gram-positive bacteria lack an outer membrane but are surrounded by layers of peptidoglycan many times thicker than is found in the Gram-negatives. Threading through these layers of peptidoglycan are long anionic polymers, called teichoic acids. The composition and organization of these envelope layers and recent insights into the mechanisms of cell envelope assembly are discussed.

/pdf/the-bacterial-cell-envelope-o3k9u4ycci.pdf

The Bacterial Cell Envelope

The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions. These proteins are ubiquitously expressed across the species, from yeast to man. The mammalian Rho-like GTPases comprise at least 10 distinct proteins: RhoA, B, C, D, and E; Rac1 and 2; RacE; Cdc42Hs, and TC10. A comparison of the amino acid sequences of the Rho proteins from various species has revealed that they are conserved in primary structure and are 50%–55% homologous to each other. Like all members of the Ras superfamily, the Rho GTPases function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. Until recently, members of the Rho subfamily were believed to be involved primarily in the regulation of cytoskeletal organization in response to extracellular growth factors. However, research from a number of laboratories over the past few years has revealed that the Rho GTPases play crucial roles in diverse cellular events such as membrane trafficking, transcriptional regulation, cell growth control, and development. Consequently, a major challenge has been to unravel the underlying molecular mechanisms by which the Rho GTPases mediate these various activities. Many targets of the Rho GTPases have now been identified and further characterization of some of them has provided major insights toward our understanding of Rho GTPase function at the molecular level. This review aims to summarize the general established principles about the Rho GTPases and some of the more recent exciting findings, hinting at novel, unanticipated functions of the Rho GTPases.

/pdf/rho-gtpases-and-signaling-networks-48wqq41h57.pdf

Rho GTPases and signaling networks

Phospholipids play multiple roles in cells by establishing the permeability barrier for cells and cell organelles, by providing the matrix for the assembly and function of a wide variety of catalytic processes, by acting as donors in the synthesis of macromolecules, and by actively influencing the functional properties of membrane-associated processes. The function, at the molecular level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in specific cellular processes is reviewed, with a focus on the results of combined molecular genetic and biochemical studies in Escherichia coli. These results are compared with primarily biochemical data supporting similar functions for these phospholipids in eukaryotic organisms. The wide range of processes in which specific involvement of phospholipids has been documented explains the need for diversity in phospholipid structure and why there are so many membrane lipids.

MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?

Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane.

The ATPase activity of secA is regulated by acidic phospholipids, secY, and the leader and mature domains of precursor proteins

PROGRESSION of proteins through the secretory pathway of eukaryotic cells involves a continuous rearrangement of macromolecular structures made up of proteins and phospholipids. The protein SEC14p is essential for transport of proteins from the yeast Golgi complex1. Independent characterization of the SEC14 gene2 and the PIT1 gene3, which encodes a phosphatidy-linositol/phosphatidylcholine transfer protein in yeast, indicated that these two genes are identical. Phospholipid transfer proteins are a class of cytosolic proteins that are ubiquitous among eukaryotic cells and are distinguished by their ability to catalyse the exchange of phospholipids between membranesin vitro4. We show here that the SEC14 and PIT1 genes are indeed identical and that the growth phenotype of a sec 14-1ts mutant extends to the inability of its transfer protein to effect phospholipid transfer in vitro4,5. These results therefore establish for the first time an in vivo function for a phospholipid transfer protein, namely a role in the compartment-specific stimulation of protein secretion.

An essential role for a phospholipid transfer protein in yeast Golgi function.

Cardiolipin (CL)-specific fluorescent dye 10-N-nonyl-acridine orange (NAO) was used to visualize CL distribution in Escherichia coli cells of different phospholipid compositions. In a filamentous mutant containing only anionic phospholipids, green fluorescent spots were observed along the filaments at approximately regular intervals. Three-dimensional image reconstruction obtained by optical sectioning and a deconvolution algorithm revealed NAO-binding domains in the plane of the cell membrane. Substantial red fluorescence emission of bound NAO supported labeling of CL-containing domains. These structures were not found in mutants deficient in CL biosynthesis. The domains were also observed mostly in the septal region and on the poles in cells of normal size with wild-type phospholipid composition.

William Dowhan

Papers

MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?

Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane.

The ATPase activity of secA is regulated by acidic phospholipids, secY, and the leader and mature domains of precursor proteins

An essential role for a phospholipid transfer protein in yeast Golgi function.

Visualization of phospholipid domains in Escherichia coli by using the cardiolipin-specific fluorescent dye 10-N-nonyl acridine orange.