Structural Studies of the Haemophilus influenzae Hia Autotransported Adhesin and of its membrane insertion partner, D15, an Omp85 homolog. (360G-Wellcome-080870_Z_06_Z)
Haemophilus influenzae is a common cause of respiratory tract disease, including otitis media, sinusitis, bronchitis, and pneumonia. Less commonly, this organism causes serious systemic disease, such as meningitis, endocarditis, and septicemia. The initial step in the pathogenesis of H. influenzae disease involves colonization of the upper respiratory mucosa. A high-molecular-weight outer-membrane protein called Hia, present in nontypable (nonencapsulated) H. influenzae, promotes attachment to the human respiratory epithelium. The Hia protein is a non-pilus adhesin and belongs to the family of autotransporter proteins. Hia is synthesized as a 114 kDa precursor protein that consists of three domains: a 49 residue N-terminal signal sequence, an internal passenger domain (residues 50-1022), and a C-terminal beta-domain (residue 1023-1098). Adherence activity is localized to the passenger domain. The protein inserts in the bacterial membrane as a trimer and remains attached in a trimeric form. Insertion of Hia in the membrane is thought to be facilitated by the integral membrane protein D15, an Omp85 homolog. This grant proposal aims at solving the structures of full-length and/or large fragments of Hia and at initiating crystallographic work on D15. These structures will provide the structural basis of Hia autotranport and insertion in and through the membrane.
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Grant Details
Amount Awarded | 243225 |
Applicant Surname | Waksman |
Approval Committee | Immunology and Infectious Disease Funding Committee |
Award Date | 2006-10-19T00:00:00+00:00 |
Financial Year | 2006/07 |
Grant Programme: Title | Project Grant |
Internal ID | 080870/Z/06/Z |
Lead Applicant | Prof Gabriel Waksman |
Other Applicant(s) | Dr Guoyu Meng |
Partnership Value | 243225 |
Planned Dates: End Date | 2010-01-31T00:00:00+00:00 |
Planned Dates: Start Date | 2007-02-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |