The IDIP framework for assessing protein function and its application to the prion protein

The quest to determine the function of a protein can represent a profound challenge. Although this task is the mandate of countless research groups, a general framework for how it can be approached is conspicuously lacking. Moreover, even expectations for when the function of a protein can be considered to be ‘known’ are not well defined. In this review, we begin by introducing concepts pertinent to the challenge of protein function assignments. We then propose a framework for inferring a protein's function from four data categories: ‘inheritance’, ‘distribution’, ‘interactions’ and ‘phenotypes’ (IDIP). We document that the functions of proteins emerge at the intersection of inferences drawn from these data categories and emphasise the benefit of considering them in an evolutionary context. We then apply this approach to the cellular prion protein (PrP^C), well known for its central role in prion diseases, whose function continues to be considered elusive by many investigators. We document that available data converge on the conclusion that the function of the prion protein is to control a critical post-translational modification of the neural cell adhesion molecule in the context of epithelial-to-mesenchymal transition and related plasticity programmes. Finally, we argue that this proposed function of PrP^C has already passed the test of time and is concordant with the IDIP framework in a way that other functions considered for this protein fail to achieve. We anticipate that the IDIP framework and the concepts analysed herein will aid the investigation of other proteins whose primary functional assignments have thus far been intractable.     

Description of Phaeobola aeris gen. nov., sp. nov (Rhizaria,Cercozoa, Euglyphida) Sheds Light on Euglyphida’s Dark Matter

The majority of Euglyphida species are characterised by shells with imbricated silica scales. Environmental surveys indicate a large unexplored diversity and recent efforts hinted at a certain diversity of yet undescribed, inconspicuous, scale-lacking Euglyphida. Here we describe Phaeobola aeris gen. nov., sp. nov. that shows a variety of morphological characters typical for the Euglyphida but lacks silica scales-instead, this species bears an agglutinated test. Neither its morphology nor phylogenetic placement allows its assignment to any currently described family. We erected the yet monospecific genus Phaeobola gen. nov., which with yet available data remain Euglyphida incertae sedis.     

Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data

Background  

Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein.     

Compatibility groups in Ascobolus immersus — an indication of speciation

Summary The mating pattern between 38 strains collected at various places in Europe and Southern India was determined. There are at least three compatibility groups: A (23 strains) and B (9 strains) comprising the European isolates, and C (6 strains), the Indian isolates. Within each compatibility group sexual reproduction is, as expected, controlled by a bipolar mechanism of homogenic incompatibility. No fertile offspring are obtained in any intergroup crossing showing that there is genetic separation by heterogenic incompatibility. However, the European group B seems to be closer related to the Indian (C) group in that sterile fruit bodies are produced between + and – mating types. An indication for a further subdivision is the occurrence of a barrage-like phenomenon between representatives of all three groups. The data thus indicate how the start of speciation may be occurring in Ascobolus immersus by means of both spatial and genetic isolation.