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".

Phonological features of Yazghulami : A field study

Yazghulami is a South-East Iranian language spoken in the Pamir area of Tajikistan by about 9000 people. This study gives an account of the phonology of the language by describing contrastive segments and their distribution and realizations, as well as describing suprasegmental features such as syllable structure and stress patterns. Field research was carried out in a community of Yazghulami speakers in Dushanbe, the capital of Tajikistan, by recording, transcribing and annotating spoken language. Yazghulami is analyzed as having 8 vowel phonemes of which one pair contrasts in length, and 36 consonant phonemes with a considerable display of palatal, velar and uvular phonemes, of which a set of three labialized plosives and three labialized fricatives is found. The syllable structure of Yazghulami allows for clusters of no more than two consonants in the onset and two in the coda; clusters in both positions do not occur in one and the same syllable. The stress generally falls on the last syllable of a word, although when nouns are inflected with suffixes, the stress instead falls on the last syllable of the stem. With these results, a foundation for further efforts to develop and increase the status of this endangered language is laid.