Identification of Extracellular Segments by Mass Spectrometry Improves Topology Prediction of Transmembrane Proteins

Transmembrane proteins play crucial role in signaling, ion transport, nutrient uptake, as well as in maintaining the dynamic equilibrium between the internal and external environment of cells. Despite their important biological functions and abundance, less than 2% of all determined structures are transmembrane proteins. Given the persisting technical difficulties associated with high resolution structure determination of transmembrane proteins, additional methods, including computational and experimental techniques remain vital in promoting our understanding of their topologies, 3D structures, functions and interactions. Here we report a method for the high-throughput determination of extracellular segments of transmembrane proteins based on the identification of surface labeled and biotin captured peptide fragments by LC/MS/MS. We show that reliable identification of extracellular protein segments increases the accuracy and reliability of existing topology prediction algorithms. Using the experimental topology data as constraints, our improved prediction tool provides accurate and reliable topology models for hundreds of human transmembrane proteins

KAT + B!

It is known that certain program transformations require a small amount of mutable state, a feature not explicitly provided by Kleene algebra with tests (KAT). In this paper we show how to axiomatically extend KAT with this extra feature in the form of mutable tests. The extension is conservative and is formulated as a general commutative coproduct construction. We give several results on deductive completeness and complexity of the system, as well as some examples of its use.Danish Council for Independent Research, Project 11-106278, ``Kleene Meets Church (KMC): Regular Expressions and Types.'