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1645 Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins

  1. Top of page
  2. 1645 Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins
  3. 1675 Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein
  4. 1697 A human sterile alpha motif domain polymerizome
  5. 1765 Validation of the detergent micelle classification for membrane protein crystals and explanation of the Matthews Graph for soluble proteins

Lidio Meireles, Mert Gur, Ahmet Bakan, and Ivet Bahar

What is the role of protein flexibility in molecular recognition and binding? Recent studies have shown that the intrinsic motions of proteins accommodate and facilitate ligand binding. Here, the authors emphasize the close agreement between experimentally observed structural changes and the collective modes or paths of motion theoretically predicted from the protein's native contact topology in the absence of substrate or ligand. An ensemble of accessible paths predictable by elastic network models, rather than preexisting states, appears to underlie the predisposition of proteins to bind their substrates.

1675 Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein

  1. Top of page
  2. 1645 Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins
  3. 1675 Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein
  4. 1697 A human sterile alpha motif domain polymerizome
  5. 1765 Validation of the detergent micelle classification for membrane protein crystals and explanation of the Matthews Graph for soluble proteins

Helen M. Saunders, Dimitri Gilis, Marianne Rooman, Yves Dehouck, Amy L. Robertson, and Stephen P. Bottomley

Polyglutamine-mediated aggregation causes nine neurodegenerative diseases. Ataxin-3 is a polyQ repeat protein consisting of a folded domain, Josephin, attached to the aggregation prone polyQ tract. Bottomley and coworkers set out to examine how changing the thermodynamic stability of the folded domain affects the polyQ mediated aggregation. Using the PoPMuSiC algorithm they altered the stability of Josephin and examined its effects upon pathogenic ataxin-3 aggregation. Their data revealed that increasing the stability of non-polyQ regions dramatically slows down polyglutamine-mediated aggregation. Together these results suggest a complex interaction between the polyQ tract and non-polyQ regions in determining the rate and extent of aggregation.

1697 A human sterile alpha motif domain polymerizome

  1. Top of page
  2. 1645 Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins
  3. 1675 Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein
  4. 1697 A human sterile alpha motif domain polymerizome
  5. 1765 Validation of the detergent micelle classification for membrane protein crystals and explanation of the Matthews Graph for soluble proteins

Mary Jane Knight, Catherine Leettola, Mari Gingery, Hao Li, and James U. Bowie

SAM domains are very common protein modules in eukaryotic cells. Many SAM domains form polymeric structures, thereby helping to build large protein complexes. Knight et al. developed a method to rapidly screen for polymerization activity and identified many new polymerizing SAM domains in the human genome. The results provide new functional insights into many important signaling and scaffolding proteins.

1765 Validation of the detergent micelle classification for membrane protein crystals and explanation of the Matthews Graph for soluble proteins

  1. Top of page
  2. 1645 Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins
  3. 1675 Flanking domain stability modulates the aggregation kinetics of a polyglutamine disease protein
  4. 1697 A human sterile alpha motif domain polymerizome
  5. 1765 Validation of the detergent micelle classification for membrane protein crystals and explanation of the Matthews Graph for soluble proteins

Georg E. Schulz

For over 40 years, protein crystallographers have reported the packing parameter VM of their crystals characterizing the solvent content. For soluble proteins, the VM distribution is a well-known graph shaped like a Gaussian with one large tail. A corresponding, but quite differently shaped distribution was recently established for integral membrane proteins. Using simple molecular models, the article reproduces both graphs quantitatively, showing that the difference is not caused by a simple addition of detergent to the solvent part, but by different contact rules. As the simulation of membrane protein crystals resulted in the observed detergent micelle fusion groups, it validates the respective classification.