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  1. Top of page
  2. 551 Structure and Function of LGR5: An enigmatic G-protein coupled receptor marking stem cells
  3. 566 An energetic scale for equilibrium H/D fractionation factors Illuminates hydrogen bond free energies in proteins
  4. 526 Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses
  5. 639 Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs
  6. 539 Advantages of proteins being disordered

Kaavya Krishna Kumar, Antony W. Burgess and Jacqueline M. Gulbis

Leucine-rich repeat-containing G-Protein Coupled Receptor 5 (LGR5) is a member of the GPCR superfamily and has attracted considerable interest in cancer biology as a stem cell marker. LGR5 is induced by Wnt signaling and provides feedback modulation. New information regarding its physiology has come to light recently: the identification of the Rspondins as high affinity LGR5 ligands, preliminary evidence of G-protein coupling to the activation of LGR5 signaling and LGR5 stimulation of cell-cell adhesion. Although early attention focused on the ectodomain, both ecto- and transmembrane domains have now been implicated in the LGR5 signal transduction processes. We provide a concise overview of recent discoveries relevant to LGR5 structural biology, ligand interactions and signaling. Structures of the LGR5 ectodomain are compared; in particular of LGR5 bound to Rspondin and a membrane associated E3 ligase (RNF43).

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  1. Top of page
  2. 551 Structure and Function of LGR5: An enigmatic G-protein coupled receptor marking stem cells
  3. 566 An energetic scale for equilibrium H/D fractionation factors Illuminates hydrogen bond free energies in proteins
  4. 526 Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses
  5. 639 Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs
  6. 539 Advantages of proteins being disordered

Zheng Cao and James U. Bowie

Hydrogen bonding is a key aspect of molecular interactions that is often subject to experimental scrutiny. Hydrogen/deuterium fractionation factors provide a particularly subtle and simple way to experimentally probe hydrogen bond contributions. Here we provide a means for using fractionation factors to measure hydrogen bond free energy, allowing us to place prior isotope effect measurements on an energetic scale. Of particular interest are backbone hydrogen bond contributions in proteins, which are hard to assess by other means. We find that there can be large changes in backbone hydrogen bond strength during conformational changes, suggesting that backbone hydrogen bonds can play an important role in protein dynamics. The energetic scale provided here should be widely applicable for assessing hydrogen bond contributions to molecular interactions.

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  1. Top of page
  2. 551 Structure and Function of LGR5: An enigmatic G-protein coupled receptor marking stem cells
  3. 566 An energetic scale for equilibrium H/D fractionation factors Illuminates hydrogen bond free energies in proteins
  4. 526 Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses
  5. 639 Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs
  6. 539 Advantages of proteins being disordered

Brian Krumm, Yan Xiang and Junpeng Deng

Interleukin-1 (IL-1) superfamily of cytokines play key roles in inflammation and regulating immunity, whose unregulated activities are linked to autoimmune diseases. The structural and functional data in the past two decades, especially from the recent studies on the ternary complex of IL-1 and its receptors, provided important clues for better understanding of the molecular mechanisms of the initiation and regulation of IL-1 superfamily cytokine signaling. These insights offer great opportunities for the rational development of inhibitors against specific cytokines for treating inflammatory diseases in the future.

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  1. Top of page
  2. 551 Structure and Function of LGR5: An enigmatic G-protein coupled receptor marking stem cells
  3. 566 An energetic scale for equilibrium H/D fractionation factors Illuminates hydrogen bond free energies in proteins
  4. 526 Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses
  5. 639 Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs
  6. 539 Advantages of proteins being disordered

Krzysztof Tarnowski, Kinga Fituch, Roman H. Szczepanowski, Michal Dadlez and Magdalena Kaus-Drobek

RACK1 is a member of the WD repeat family of proteins and is involved in multiple fundamental cellular processes. Here, Tarnowski et al used hydrogen-deuterium exchange mass spectrometry (HDXMS) to probe the dynamics of RACK1 orthologs. By mapping flexible and rigid regions of RACK1 proteins, Tarnowski, et al were able to identify regions of flexibility that can be associated with ligand binding or posttranslational modifications. In addition, authors performed analysis on H-D exchange kinetics of human RACK1 and found that amide protons in some regions exchanged at least 1000-fold faster than in others. They proved that HDXMS is a useful tool for mapping protein-protein interactions, as exemplified by their analysis of the dimerization mode of yeast RACK1.

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  1. Top of page
  2. 551 Structure and Function of LGR5: An enigmatic G-protein coupled receptor marking stem cells
  3. 566 An energetic scale for equilibrium H/D fractionation factors Illuminates hydrogen bond free energies in proteins
  4. 526 Structural biology of the IL-1 superfamily: Key cytokines in the regulation of immune and inflammatory responses
  5. 639 Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs
  6. 539 Advantages of proteins being disordered

Zhirong Liu and Yongqi Huang

The unique three-dimensional structure of a protein has long been held as a prerequisite of its biological function. However, more and more “special” proteins have been discovered which do not have ordered structures in the free state under physiological conditions but still possess biological functions. They are termed as intrinsically disordered proteins (IDPs). IDPs are abundant in all species and perform functions complementary to those of ordered proteins. They are persistent in evolution either. Therefore, they are expected to possess some advantages (and disadvantages) over ordered proteins. In this review, we summarize and survey nine possible advantages of IDPs.

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