151 research outputs found
Structure and Topology of the 114kDa Serca-Sarcolipin Complex by Solid State NMR Spectroscopy
Structural Dynamics of Phosphorylated Pentameric Phospholamban in Lipid Membranes using a Combination of Solution and Solid-State NMR Spectroscopy
Hybrid Solution and Solid-State NMR Analysis of SERCA/Phospholamban Interactions in lipid membranes: From Structural Dynamics to Function
Solution and Solid-State NMR Analysis of Phosphorylated and Pseudo-Phosphorylated Phospholamban
Cushing’s syndrome driver mutation disrupts protein kinase A allosteric network, altering both regulation and substrate specificity
Structural basis of synaptic vesicle assembly promoted by α-synuclein.
α-synuclein (αS) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson's disease. Although the specific function of αS is still unclear, a general consensus is forming that it has a key role in regulating the process of neurotransmitter release, which is associated with the mediation of synaptic vesicle interactions and assembly. Here we report the analysis of wild-type αS and two mutational variants linked to familial Parkinson's disease to describe the structural basis of a molecular mechanism enabling αS to induce the clustering of synaptic vesicles. We provide support for this 'double-anchor' mechanism by rationally designing and experimentally testing a further mutational variant of αS engineered to promote stronger interactions between synaptic vesicles. Our results characterize the nature of the active conformations of αS that mediate the clustering of synaptic vesicles, and indicate their relevance in both functional and pathological contexts
The TLQP-21 Peptide Activates the G-Protein-Coupled Receptor C3aR1 via a Folding-upon-Binding Mechanism
TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled-receptor (GPCR) Complement-3a-Receptor1 (C3aR1). So far, the mechanisms of TLQP-21-induced receptor activation remained unexplored. Here, we report that TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition, adopting an α-helical conformation, upon targeting cells expressing the C3aR1. We determined that the hot spots for TLQP-21 are located at the C-terminus, with mutations in the last four amino acids progressively reducing the bioactivity and, a single site mutation (R21A) or C-terminal amidation abolishing its function completely. Interestingly, the human TLQP-21 sequence carrying a S20A substitution activates the human C3aR1 receptor with lower potency compared to the rodent sequence. These studies reveal the mechanism of action of TLQP-21 and provide molecular templates for designing agonists and antagonists to modulate C3aR1 functions
Theoretical Analysis of Residual Dipolar Coupling Patterns in Regular Secondary Structures of Proteins
Phospholamban Phosphorylation Alters its Conformational Equilibrium to Regulate SERCA Activity
- …