Topic
Structural biology
About: Structural biology is a research topic. Over the lifetime, 2206 publications have been published within this topic receiving 126070 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: The minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system is defined and a novel type of self-sustained protein translocation across membranes is established, revealing the molecular basis of the unconventional secretory pathway of F GF2.
Abstract: FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules. Vectorial translocation of FGF2 across the membrane is governed by sequential and mutually exclusive interactions with PI(4,5)P2 and heparan sulfates on opposing sides of the membrane. Based on atomistic molecular dynamics simulations, we propose a mechanism that drives PI(4,5)P2 dependent oligomerization of FGF2. Our combined findings establish a novel type of self-sustained protein translocation across membranes revealing the molecular basis of the unconventional secretory pathway of FGF2.
62 citations
TL;DR: The crystal structure of a soluble form of human soluble CD73 (sCD73) at 2.2 Å resolution will aid the design of inhibitors or activator molecules for the treatment of several diseases and prove useful in explaining the possible roles of single nucleotide polymorphisms in physiology and disease.
Abstract: CD73 is a dimeric ecto-5′-nucleotidase that is expressed on the exterior side of the plasma membrane. CD73 has important regulatory functions in the extracellular metabolism of certain nucleoside monophosphates, in particular adenosine monophosphate, and has been linked to a number of pathological conditions such as cancer and myocardial ischaemia. Here, we present the crystal structure of a soluble form of human soluble CD73 (sCD73) at 2.2 A resolution, a truncated form of CD73 that retains ecto-5′-nucleotidase activity. With this structure we obtained insight into the dimerisation of CD73, active site architecture, and a sense of secondary modifications of the protein. The crystal structure reveals a conserved loop that is directly involved in the dimer-dimer interaction showing that the two subunits of the dimer are not linked by disulfide bridges. Using biophotonic microarray imaging we were able to confirm glycosylation of the enzyme and show that the enzyme is decorated with a variety of oligosaccharide structures. The crystal structure of sCD73 will aid the design of inhibitors or activator molecules for the treatment of several diseases and prove useful in explaining the possible roles of single nucleotide polymorphisms in physiology and disease.
62 citations
TL;DR: Recent advances in the understanding of the structural biology of the writers, readers, and erasers of ADP-ribosylation are reviewed.
62 citations
TL;DR: In this article, a global protein structural readout based on limited proteolysis-mass spectrometry (LiP-MS) was used to detect functional alterations in bacteria undergoing nutrient adaptation and in yeast responding to acute stress.
62 citations
TL;DR: This analysis provides novel insights into ligand binding, allosteric modulation, and signaling of the AR family by mapping onto the relevant crystal structures all site-directed mutagenesis data, curated and deposited at the GPCR database.
62 citations