Abstract
Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane
1
. Here we show that a supercomplex containing all four respiratory chain components ...contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I–II–III
2
–IV
2
supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.
Light-driven sodium pumps actively transport small cations across cellular membranes
. These pumps are used by microorganisms to convert light into membrane potential and have become useful ...optogenetic tools with applications in neuroscience. Although the resting state structures of the prototypical sodium pump Krokinobacter eikastus rhodopsin 2 (KR2) have been solved
, it is unclear how structural alterations over time allow sodium to be translocated against a concentration gradient. Here, using the Swiss X-ray Free Electron Laser
, we have collected serial crystallographic data at ten pump-probe delays from femtoseconds to milliseconds. High-resolution structural snapshots throughout the KR2 photocycle show how retinal isomerization is completed on the femtosecond timescale and changes the local structure of the binding pocket in the early nanoseconds. Subsequent rearrangements and deprotonation of the retinal Schiff base open an electrostatic gate in microseconds. Structural and spectroscopic data, in combination with quantum chemical calculations, indicate that a sodium ion binds transiently close to the retinal within one millisecond. In the last structural intermediate, at 20 milliseconds after activation, we identified a potential second sodium-binding site close to the extracellular exit. These results provide direct molecular insight into the dynamics of active cation transport across biological membranes.
Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane
. Here we show that a supercomplex containing all four respiratory chain components contributes ...to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I-II-III
-IV
supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.
The structure of the rhodopsin/mini-G
o
complex reveals new insights on G protein selectivity.
Selective coupling of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors ...(GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-G
o
protein. The conformation of the receptor is identical to all previous structures of active rhodopsin, including the complex with arrestin. Thus, rhodopsin seems to adopt predominantly one thermodynamically stable active conformation, effectively acting like a “structural switch,” allowing for maximum efficiency in the visual system. Furthermore, our analysis of the well-defined GPCR–G protein interface suggests that the precise position of the carboxyl-terminal “hook-like” element of the G protein (its four last residues) relative to the TM7/helix 8 (H8) joint of the receptor is a significant determinant in selective G protein activation.
Selective coupling of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried ...by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-G
protein. The conformation of the receptor is identical to all previous structures of active rhodopsin, including the complex with arrestin. Thus, rhodopsin seems to adopt predominantly one thermodynamically stable active conformation, effectively acting like a "structural switch," allowing for maximum efficiency in the visual system. Furthermore, our analysis of the well-defined GPCR-G protein interface suggests that the precise position of the carboxyl-terminal "hook-like" element of the G protein (its four last residues) relative to the TM7/helix 8 (H8) joint of the receptor is a significant determinant in selective G protein activation.
In the present work, different biopolymer blend scaffolds based on the silk protein fibroin from Bombyx mori (BM) were prepared via freeze‐drying method. The chemical, structural, and mechanical ...properties of the three dimensional (3D) porous silk fibroin (SF) composite scaffolds of gelatin, collagen, and chitosan as well as SF from Antheraea pernyi (AP) and the recombinant spider silk protein spidroin (SSP1) have been systematically investigated, followed by cell culture experiments with epithelial prostate cancer cells (LNCaP) up to 14 days. Compared to the pure SF scaffold of BM, the blend scaffolds differ in porous morphology, elasticity, swelling behavior, and biochemical composition. The new composite scaffold with SSP1 showed an increased swelling degree and soft tissue like elastic properties. Whereas, in vitro cultivation of LNCaP cells demonstrated an increased growth behavior and spheroid formation within chitosan blended scaffolds based on its remarkable porosity, which supports nutrient supply matrix. Results of this study suggest that silk fibroin matrices are sufficient and certain SF composite scaffolds even improve 3D cell cultivation for prostate cancer research compared to matrices based on pure biomaterials or synthetic polymers.
Years of Life Lost to Death Wengler, Annelene; Rommel, Alexander; Plaß, Dietrich ...
Deutsches Ärzteblatt international,
03/2021, Letnik:
118, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Knowing which diseases and causes of death account for most of the years of life lost (YLL) can help to better target appropriate prevention and intervention measures. The YLL in Germany for specific ...causes of death were estimated as part of the BURDEN 2020 project at the Robert Koch Institute.
Data from cause-of-death statistics were used for the analysis. ICD codes were grouped into causes of death categories at different levels of disaggregation. The YLL were estimated by combining each cause of death with the remaining life expectancy at the age of death. Deaths and YLL were compared by sex, age category, and regional distribution.
Approximately 11.6 million years were estimated to be lost in Germany in 2017, of which 42.8% were lost by women and 57.2% by men. The largest number of YLL were due to (malignant) neoplasms (35.2%), followed by cardiovascular diseases (27.6%), gastrointestinal diseases (5.8%), and neurological diseases (5.7%). Deaths at younger ages had a greater impact on population health if expressed in YLL: the death share of persons under age 65 was 14.7%, but the years of life lost in this age group amounted to 38.3% of all YLL. The most common causes of death in this group include accidents, self-injury and violence, malignant neoplasms, and alcohol-related diseases.
A large proportion of YLL is borne by young and middle-aged persons. These findings emphasize the need to introduce preventive strategies early in life to reduce the YLL at younger ages, as well as to prevent risk factors for diseases in older ages.
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