Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.693879
Title: Structural and functional studies of the Als3 adhesin from Candida albicans
Author: Lin, Jing
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Abstract:
Candida spp. are the fourth most common cause of nosocomial bloodstream infections. Candida albicans, a commensal microbe, causes 90% Candidiasis. The Als family (agglutinin-like sequences), a key factor in C. albicans pathogenesis, encodes large cell-surface glycoproteins which are involved in host-pathogen interactions and morphogenesis. Members of the Als protein family bind peptides with broad specificity and have been implicated in the binding of host cell surface and extracellular matrix proteins. Recent work shows that Als3 is essential for C. albicans adhesion, and it can also work like an invasin and induce endocytosis in normal host cells. Previous study from this laboratory shows that the N-terminal domain of Als1 is able to bind peptides and fold into the same overall topology observed for the two-domain N-terminal fragment of the clumping factor (ClfA) from Staphylococcus aureus. This observation and the promiscuous ligand specificity displayed by the Als adhesins opens the possibility of a common mechanism of adhesion shared by bacterial and fungal pathogens based on the binding of unstructured polypeptides. Such a mechanism would provide a unique mode of binding, as it circumvents the strict surface complementarity observed in most pathogen/host cell interactions. The project aims to focus on the structural and functional properties of Als3 and unravel the binding mechanism and range of affinities to ligands. Three different Als3 structures were solved during this project. Firstly, the crystal structure of the peptide-free form of Als3299 was solved at 1.8 ?. After that, the crystal structure of the bound form of Als3299 was available at 1.4 ?, which illustrates a promising possibility of Als3 binding mechanism. The third structure, Triple-Mutant Als3 (K59M, V116A, and Y298F), was diffracted well under micro-focus beam in Diamond light source, UK. Those three structures provide valuable information to elucidate the structure, function, and binding mode of Als3 in different angles.
Supervisor: Cota Segura, Ernesto Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.693879  DOI: Not available
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