Theoretical studies of Membrane Proteins : Properties, Prediction Methods and Genome-wide analysis

Membrane proteins are a large and important class of proteins. They are responsible for several of the key functions in a living cell, e.g. transport of nutrients and ions, cell-cell signaling, and cell-cell adhesion. Despite their importance it has not been possible to study their structure and organization in much detail because of the difficulty to obtain 3D structures. In this thesis theoretical studies of membrane protein sequences and structures have been carried out by analyzing existing experimental data. The data comes from several sources including sequence databases, genome sequencing projects, and 3D structures. Prediction of the membrane spanning regions by hydrophobicity analysis is a key technique used in several of the studies. A novel method for this is also presented and compared to other methods. The primary questions addressed in the thesis are: What properties are common to all membrane proteins? What is the overall architecture of a membrane protein? What properties govern the integration into the membrane? How many membrane proteins are there and how are they distributed in different organisms? Several of the findings have now been backed up by experiments. An analysis of the large family of G-protein coupled receptors pinpoints differences in length and amino acid composition of loops between proteins with and without a signal peptide and also differences between extra- and intracellular loops. Known 3D structures of membrane proteins have been studied in terms of hydrophobicity, distribution of secondary structure and amino acid types, position specific residue variability, and differences between loops and membrane spanning regions. An analysis of several fully and partially sequenced genomes from eukaryotes, prokaryotes, and archaea has been carried out. Several differences in the membrane protein content between organisms were found, the most important being the total number of membrane proteins and the distribution of membrane proteins with a given number of transmembrane segments. Of the properties that were found to be similar in all organisms, the most obvious is the bias in the distribution of positive charges between the extra- and intracellular loops. Finally, an analysis of homologues to membrane proteins with known topology uncovered two related, multi-spanning proteins with opposite predicted orientations. The predicted topologies were verified experimentally, providing a first example of "divergent topology evolution".

The coronal heating problem

The heating of the solar corona has been investigated during four of decades and several mechanisms able to produce heating have been proposed. It has until now not been possible to produce quantitative estimates that would establish any of these heating mechanism as the most important in the solar corona. In order to investigate which heating mechanism is the most important, a more detailed approach is needed. In this thesis, the heating problem is approached ”ab initio”, using well observed facts and including realistic physics in a 3D magneto-hydrodynamic simulation of a small part of the solar atmosphere. The ”engine” of the heating mechanism is the solar photospheric velocity field, that braids the magnetic field into a configuration where energy has to be dissipated. The initial magnetic field is taken from an observation of a typical magnetic active region scaled down to fit inside the computational domain. The driving velocity field is generated by an algorithm that reproduces the statistical and geometrical fingerprints of solar granulation. Using a standard model atmosphere as the thermal initial condition, the simulation goes through a short startup phase, where the initial thermal stratification is quickly forgotten, after which the simulation stabilizes in statistical equilibrium. In this state, the magnetic field is able to dissipate the same amount of energy as is estimated to be lost through radiation, which is the main energy loss mechanism in the solar corona. The simulation produces heating that is intermittent on the smallest resolved scales and hot loops similar to those observed through narrow band filters in the ultra violet. Other observed characteristics of the heating are reproduced, as well as a coronal temperature of roughly one million K. Because of the ab initio approach, the amount of heating produced in these simulations represents a lower limit to coronal heating and the conclusion is that such heating of the corona is unavoidable.