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In this thesis we implement an ensemble of sequence analysis strategies aimed at identifying functional and structural protein features. The first part of this work was dedicated to two case studies of specific proteins analyzed to provide candidate functional positions for experimental validation: the protein alpha-synuclein (αsyn) and the alanine racemases protein family. In the case of αsyn, the objective was to predict its aggregation prone regions. For the alanine racemase protein family, the scope was to predict sites responsible for substrate specificity. In these two studies, computational predictions allowed systematically exploring potentially functionally relevant protein sites in an efficient manner that may not be possible to implement with traditional experimental approaches. Our strategy provided a powerful forecasting tool for the selection of candidate sites to be later verified experimentally. In the second part, we analyze the role of intrinsic disorder (ID) as a modulator of protein function in different organisms and cellular processes, which is largely unexplored. As key components of the diverse cellular pathways, disordered proteins are often involved in many diseases, including cancer and neurodegenerative diseases. Thus, there is an impeding need to unveil the general principles underlying the role of ID in proteins. We provide a multi-scale analysis of the involvement of ID in protein function starting with a large-scale analysis at genomic level of the role of ID in Arabidopsis, zooming in into the specific processes of vesicular trafficking in Human and yeast, and finally focusing on specific proteins of diverse organisms. The results of this thesis provide a better understanding of the functional roles mediated by ID in different organisms and biological processes, such as acting as flexible linkers connecting structured domains, mediating protein-protein interactions, and assisting the quick assembly of large macromolecular complexes. In addition, we present evidence of the use of ID as a mechanism to increase the complexity of protein and biological networks, and as a means to increase the adaptability of proteins in specific processes. Thus, our results contribute to elucidating the relationship between network and organismal complexity and ID, while they also provide evidence of the evolutionary advantages offered by ID.

Les PME représentent en France et en Turquie près de la totalité des entreprises existantes et jouent un rôle très important dans la régulation de la vie économique et sociale de ces pays. Afin de les protéger mais surtout de les inciter à œuvrer davantage pour une performance d’ordre global, l’action des dirigeants de PME doit être orientée vers une gouvernance socialement responsable. Pour parvenir à cette fin, des moyens empruntés aux règles de la « corporate governance » doivent être adoptés par ces derniers. Toutefois, ces règles de management, prévues à l’origine pour discipliner l’action des dirigeants des grandes firmes américaines de type managérial, sont inadaptées aux PME de type entrepreneurial et familial ainsi qu’au contexte dans lequel cette catégorie d’entreprises évolue. Les dirigeants de PME éprouvent en effet de grandes difficultés à mobiliser des fonds. Ils se doivent d’être pragmatiques pour la pérennité du groupement. C’est donc naturellement qu’ils songent à performer en termes économique avant de songer à performer en termes social ou sociétal. De plus, de nombreux mécanismes de gouvernance ne prennent pas en compte les spécificités organisationnelles et fonctionnelles de cette catégorie d’entreprises. Les dirigeants de PME évoluent dans un contexte proxémique fort marqué par l’informalité des relations avec les « stakeholders ». Peu visibles du grand public, ces entreprises agissent souvent dans un rayon d’activité locale voire régionale. Les dirigeants sont proches de leurs salariés, de leurs fournisseurs et créanciers, de leurs associés ainsi que de leurs clients. La propriété du capital est peu diluée de telle sorte que les fonctions de propriété, de direction et de contrôle sont souvent réunies dans les mains d’une personne forte (le dirigeant-propriétaire) ou de ses proches. Dans ces conditions, les principes de gouvernement d’entreprise tels qu’ils existent sont difficiles à mettre en œuvre par les dirigeants de PME si bien que les modes de gouvernance qu’ils adoptent sont peu influencés par la gouvernance d’entreprise et ses mécanismes. / In France and Turkey SMEs make up nearly all current enterprises and play a very important role in the regulation of economic and social life in both countries. In order to protect them, but above all, in order to encourage them to adopt more global performance, the action of SME managers has to be oriented towards socialy responsable governance. To achieve this, they have to adopt the rules of corporate governance. However, these management rules, originally intented to control the action of the managers of big US managerial firms, are not adapted to family and entrepreneurial SMEs and to the context in which this particular category of enterprise evolves. Indeed, SME managers have many difficulties to leverage private funds.They have to adopt a pragmatic approach to ensure the existence of their enterprises. It is quite normal, therefore, for them to do business in economic terms before considering social relations and societal questions. Moreover, many mechanisms of corporate governance don’t take into account the organizational and functional characteristics of this particular category of enterprise. SME managers work in a strong context of proximity characterised by the informality of relations with stakeholders. Such enterprises, since they are barely visible to the general public, often work localy or regionaly. Managers are close to their employees, suppliers and creditors, associates and customers. The ownership of capital property is not diluted very much so that the functions of ownership, management and control are often all in the hands of one strong individual (the owner-manager) or his/her relatives. In these conditions, the principles of corporate governance, as they exist today, are not easily implemented by SMEs managers to the extent that the modes of governance they adopt are barely influenced by corporate governance and its mechanisms.