- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Malaria Research and Control
- Drug Transport and Resistance Mechanisms
- Escherichia coli research studies
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- Tuberculosis Research and Epidemiology
- Lipid Membrane Structure and Behavior
- Bacterial Infections and Vaccines
- Antibiotics Pharmacokinetics and Efficacy
- Urinary Tract Infections Management
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- Trace Elements in Health
- Neonatal Health and Biochemistry
- Cell Adhesion Molecules Research
- ATP Synthase and ATPases Research
- Ion Transport and Channel Regulation
- Renal and related cancers
- Hemoglobinopathies and Related Disorders
- Ion channel regulation and function
Case Western Reserve University
2020-2024
University School
2020-2024
Sichuan University
2024
West China Hospital of Sichuan University
2024
Neisseria gonorrhoeae is an obligate human pathogen and causative agent of the sexually transmitted infection (STI) gonorrhea. The most predominant clinically important multidrug efflux system in N. multiple transferrable resistance (Mtr) pump, which mediates to a number different classes structurally diverse antimicrobial agents, including used antibiotics (e.g., β-lactams macrolides), dyes, detergents host-derived antimicrobials cationic peptides bile salts). Recently, it has been found...
The mycobacterial membrane protein large 3 (MmpL3) transporter is essential and required for shuttling the lipid trehalose monomycolate (TMM), a precursor of mycolic acid (MA)-containing dimycolate (TDM) mycolyl arabinogalactan peptidoglycan (mAGP), in Mycobacterium species, including tuberculosis smegmatis . However, mechanism that MmpL3 uses to facilitate transport fatty acids lipidic elements cell wall remains elusive. Here, we report 7 structures M its unbound state complex with...
We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) define its composition. From this sample we identified simultaneously determined high-resolution structural information for ten unique enzymes involved in diverse cellular processes. Notably, the structure of endoplasmic bifunctional protein H6PD, where N- C-terminal domains independently possess glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase enzymatic activity,...
RND efflux pumps can export numerous antimicrobials that enter Gram-negative bacteria, and their action reduce the efficacy of antibiotics provide decreased susceptibility to various host antimicrobials. Here, we identified a c ationic ntibiotic- s ensitizing p eptide (CASP) binds within periplasmic cleft an transporter protein (MtrD) produced by Neisseria gonorrhoeae .
The Na-K-2Cl cotransporter-1 (NKCC1) is an electroneutral Na+-dependent transporter responsible for simultaneously translocating Na+, K+, and Cl- ions into cells. In human tissue, NKCC1 plays a critical role in regulating cytoplasmic volume, fluid intake, chloride homeostasis, cell polarity. Here, we report four structures of (hNKCC1), both the absence presence loop diuretic (bumetanide or furosemide), using single-particle cryo-electron microscopy. These allow us to directly observe various...
Gram-negative bacteria utilize the resistance-nodulation-cell division (RND) superfamily of efflux pumps to expel a variety toxic compounds from cell. The Escherichia coli CusA membrane protein, which recognizes and extrudes biocidal Cu(I) Ag(I) ions, belongs heavy-metal (HME) subfamily RND pumps. We here report four structures trimeric pump in presence using single-particle cryo-electron microscopy (cryo-EM). discover that different protomers within trimer are able bind ions simultaneously....
The ability to investigate tissues and organs through an integrated systems biology approach has been thought be unobtainable in the field of structural biology, where techniques mainly focus on a particular biomacromolecule interest. Here we report use cryo-electron microscopy (cryo-EM) define composition raw human kidney microsomal lysate. We simultaneously identify solve cryo-EM structures four distinct enzymes whose functions have linked protein biosynthesis quality control, retinoic...
The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it responsible for catalyzing exchange bicarbonate and chloride anions across plasma membrane. To elucidate structural mechanism transporter, detergent solubilized human ghost reconstituted in nanodiscs was applied to cryo-EM holey carbon grid define its composition. With this approach, we identified determined information transporter. Here, present 5 different structures transmembrane domain...
Malaria is an extremely devastating parasitic infection that kills over half a million people each year. It the leading cause of death in many developing countries, part, due to lack resources and readily available therapeutics. Unfortunately, most prevalent deadliest causative agent malaria, Plasmodium falciparum, has developed resistance nearly all currently antimalarial drugs. The P. falciparum Niemann-Pick Type C1-related (PfNCR1) transporter been identified as druggable target, it...
Platelets fulfill their essential physiological roles sensing the extracellular environment through membrane proteins. The native provides regulatory cues that impact protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible obtain atomic-level-resolution crude...
Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, most deadliest causative agent malaria, Plasmodium falciparum , has developed resistance to nearly all currently available antimalarial drugs. The P. Niemann-Pick type C1–related (PfNCR1) transporter been identified as druggable target, but its structure and detailed molecular mechanism are not yet available. Here, we present three structures PfNCR1 with without functional...
Dicrostonyx groenlandicus (collared