Biophysics Reports

http://link.springer.com/journal/41048

List of Papers (Total 48)

Molecular architecture of mouse and human pancreatic zymogen granules: protein components and their copy numbers

A molecular model of pancreatic zymogen granule (ZG) is critical for understanding its functions. We have extensively characterized the composition and membrane topology of rat ZG proteins. In this study, we report the development of targeted proteomics approaches to quantify representative mouse and human ZG proteins using LC-SRM and heavy isotope-labeled synthetic peptides. The...

Theoretical model and characteristics of mitochondrial thermogenesis

Based on the first law of thermodynamics and the thermal diffusion equation, the deduced theoretical model of mitochondrial thermogenesis satisfies the Laplace equation and is a special case of the thermal diffusion equation. The model settles the long-standing question of the ability to increase cellular temperature by endogenous thermogenesis and explains the thermogenic...

Identification of natural products as novel ligands for the human 5-HT2C receptor

G protein-coupled receptors (GPCRs) constitute the largest human protein family with over 800 members, which are implicated in many important medical conditions. Serotonin receptors belong to the aminergic GPCR subfamily and play important roles in physiological and psychological activities. Structural biology studies have revealed the structures of many GPCRs in atomic details...

PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway

Insulin release by pancreatic β cells plays a key role in regulating blood glucose levels in humans, and to understand the mechanism for insulin secretion may reveal therapeutic strategies for diabetes. We found that PI4KIIα transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose levels than wild-type mice. Glucose-stimulated insulin secretion was...

Docking-based inverse virtual screening: methods, applications, and challenges

Identifying potential protein targets for a small-compound ligand query is crucial to the process of drug development. However, there are tens of thousands of proteins in human alone, and it is almost impossible to scan all the existing proteins for a query ligand using current experimental methods. Recently, a computational technology called docking-based inverse virtual...

Protocol for analyzing protein ensemble structures from chemical cross-links using DynaXL

Chemical cross-linking coupled with mass spectroscopy (CXMS) is a powerful technique for investigating protein structures. CXMS has been mostly used to characterize the predominant structure for a protein, whereas cross-links incompatible with a unique structure of a protein or a protein complex are often discarded. We have recently shown that the so-called over-length cross...

Determining the target protein localization in 3D using the combination of FIB-SEM and APEX2

Determining the cellular localization of proteins of interest at nanometer resolution is necessary for elucidating their functions. Besides super-resolution fluorescence microscopy, conventional electron microscopy (EM) combined with immunolabeling or clonable EM tags provides a unique approach to correlate protein localization information and cellular ultrastructural information...

Energy coupling mechanisms of AcrB-like RND transporters

Prokaryotic AcrB-like proteins belong to a family of transporters of the RND superfamily, and as main contributing factor to multidrug resistance pose a tremendous threat to future human health. A unique feature of AcrB transporters is the presence of two separate domains responsible for carrying substrate and generating energy. Significant progress has been made in elucidating...

Accelerating electron tomography reconstruction algorithm ICON with GPU

Electron tomography (ET) plays an important role in studying in situ cell ultrastructure in three-dimensional space. Due to limited tilt angles, ET reconstruction always suffers from the “missing wedge” problem. With a validation procedure, iterative compressed-sensing optimized NUFFT reconstruction (ICON) demonstrates its power in the restoration of validated missing information...

The advent of structural biology in situ by single particle cryo-electron tomography

Single particle tomography (SPT), also known as subtomogram averaging, is a powerful technique uniquely poised to address questions in structural biology that are not amenable to more traditional approaches like X-ray crystallography, nuclear magnetic resonance, and conventional cryoEM single particle analysis. Owing to its potential for in situ structural biology at subnanometer...

Particle segmentation algorithm for flexible single particle reconstruction

As single particle cryo-electron microscopy has evolved to a new era of atomic resolution, sample heterogeneity still imposes a major limit to the resolution of many macromolecular complexes, especially those with continuous conformational flexibility. Here, we describe a particle segmentation algorithm towards solving structures of molecules composed of several parts that are...

Dye-based mito-thermometry and its application in thermogenesis of brown adipocytes

Mitochondrion is the main intracellular site for thermogenesis and attractive energy expenditure targeting for obesity therapy. Here, we develop a method of mitochondrial thermometry based on Rhodamine B methyl ester, which equilibrates as a thermosensitive mixture of nonfluorescent and fluorescent resonance forms. Using this approach, we are able to demonstrate that the efficacy...

Choosing proper fluorescent dyes, proteins, and imaging techniques to study mitochondrial dynamics in mammalian cells

Mitochondrial dynamics refers to the processes maintaining mitochondrial homeostasis, including mitochondrial fission, fusion, transport, biogenesis, and mitophagy. Mitochondrial dynamics is essential for maintaining the metabolic function of mitochondria as well as their regulatory roles in cell signaling. In this review, we summarize the recently developed imaging techniques...

Using integrated correlative cryo-light and electron microscopy to directly observe syntaphilin-immobilized neuronal mitochondria in situ

Correlative cryo-fluorescence and cryo-electron microscopy (cryo-CLEM) system has been fast becoming a powerful technique with the advantage to allow the fluorescent labeling and direct visualization of the close-to-physiologic ultrastructure in cells at the same time, offering unique insights into the ultrastructure with specific cellular function. There have been various...

Class C G protein-coupled receptors: reviving old couples with new partners

G protein-coupled receptors (GPCRs) are key players in cell communication and are encoded by the largest family in our genome. As such, GPCRs represent the main targets in drug development programs. Sequence analysis revealed several classes of GPCRs: the class A rhodopsin-like receptors represent the majority, the class B includes the secretin-like and adhesion GPCRs, the class...

Using 3dRPC for RNA–protein complex structure prediction

3dRPC is a computational method designed for three-dimensional RNA–protein complex structure prediction. Starting from a protein structure and a RNA structure, 3dRPC first generates presumptive complex structures by RPDOCK and then evaluates the structures by RPRANK. RPDOCK is an FFT-based docking algorithm that takes features of RNA–protein interactions into consideration, and...

MetaDP: a comprehensive web server for disease prediction of 16S rRNA metagenomic datasets

High-throughput sequencing-based metagenomics has garnered considerable interest in recent years. Numerous methods and tools have been developed for the analysis of metagenomic data. However, it is still a daunting task to install a large number of tools and complete a complicated analysis, especially for researchers with minimal bioinformatics backgrounds. To address this...

Simulated microgravity potentiates generation of reactive oxygen species in cells

Microgravity (MG) and space radiation are two major environmental factors of space environment. Ionizing radiation generates reactive oxygen species (ROS) which plays a key role in radiation-induced DNA damage. Interestingly, simulated microgravity (SMG) also increases ROS production in various cell types. Thus, it is important to detect whether SMG could potentiate ROS...

Regulation of metabolism by the Mediator complex

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in...

Uniporter substrate binding and transport: reformulating mechanistic questions

Transporters are involved in material transport, signaling, and energy input in all living cells. One of the fundamental questions about transporters is concerned with the precise role of their substrate in driving the transport process. This is particularly important for uniporters, which must utilize the chemical potential of substrate as the only energy source driving the...

Crystal structures of MdfA complexed with acetylcholine and inhibitor reserpine

The DHA12 family of transporters contains a number of prokaryotic and eukaryote membrane proteins. Some of these proteins share conserved sites intrinsic to substrate recognition, structural stabilization and conformational changes. For this study, we chose the MdfA transporter as a model DHA12 protein to study some general characteristics of the vesicular neurotransmitter...

Structure determination of a human virus by the combination of cryo-EM and X-ray crystallography

Virus 3D atomic structures provide insight into our understanding of viral life cycles and the development of antiviral drugs. X-ray crystallography and cryo-EM have been used to determine the atomic structure of viruses. However, limited availability of biological samples, biosafety issues due to virus infection, and sometimes inherent characteristics of viruses, pose...

Opinion: hazards faced by macromolecules when confined to thin aqueous films

Samples prepared for single-particle electron cryo-microscopy (cryo-EM) necessarily have a very high surface-to-volume ratio during the short period of time between thinning and vitrification. During this time, there is an obvious risk that macromolecules of interest may adsorb to the air–water interface with a preferred orientation, or that they may even become partially or...

Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging

The integrin family comprises 24 transmembrane receptors, each a heterodimeric combination of one of 18α and one of 8β subunits. Their main function is to integrate the cell adhesion and interaction with the extracellular microenvironment with the intracellular signaling and cytoskeletal rearrangement through transmitting signals across the cell membrane upon ligand binding...