3H09

The structure of Haemophilus influenzae IgA1 protease

Summary for 3H09

• Entry DOI: 10.2210/pdb3h09/pdb
• Descriptor: Immunoglobulin A1 protease, ACETATE ION, MALONIC ACID, ... (5 entities in total)
• Functional Keywords: serine protease, immunoglobulin a1, beta helix, hydrolase, membrane, protease, secreted, transmembrane, virulence, zymogen
• Biological source: Haemophilus influenzae
• Cellular location: Immunoglobulin A1 protease autotransporter: Periplasm . Immunoglobulin A1 protease: Secreted. Immunoglobulin A1 protease translocator: Cell outer membrane ; Multi-pass membrane protein : P44969
• Total number of polymer chains: 2
• Total formula weight: 218453.11

Authors

Johnson, T.A.,Qiu, J.,Plaut, A.G.,Holyoak, T. (deposition date: 2009-04-08, release date: 2009-04-21, Last modification date: 2023-09-06)

Primary citation

Johnson, T.A.,Qiu, J.,Plaut, A.G.,Holyoak, T.
Active-Site Gating Regulates Substrate Selectivity in a Chymotrypsin-Like Serine Protease The Structure of Haemophilus influenzae Immunoglobulin A1 Protease.
J.Mol.Biol., 389:559-574, 2009

PubMed Abstract: We report here the first structure of a member of the immunoglobulin A protease (IgAP) family at 1.75-A resolution. This protease is a founding member of the type V (autotransporter) secretion system and is considered a virulence determinant among the bacteria expressing the enzyme. The structure of the enzyme fits that of a classic autotransporter in which several unique domains necessary for protein function are appended to a central, 100-A-long beta-helical domain. The N-terminal domain of the IgAP is found to possess a chymotrypsin-like fold. However, this catalytic domain contains a unique loop D that extends over the active site acting as a lid, gating substrate access. The data presented provide a structural basis for the known ability of IgAPs to cleave only the proline/serine/threonine-rich hinge peptide unique to IgA1 (isotype 1) in the context of the intact fold of the immunoglobulin. Based upon the structural data, as well as molecular modeling, a model suggesting that the unique extended loop D in this IgAP sterically occludes the active-site binding cleft in the absence of immunoglobulin binding is presented. Only in the context of binding of the IgA1-Fc domain in a valley formed between the N-terminal protease domain and another domain appended to the beta-helix spine (domain 2) is the lid stabilized in an open conformation. The stabilization of this open conformation through Fc association subsequently allows access of the hinge peptide to the active site, resulting in recognition and cleavage of the substrate.

PubMed: 19393662
DOI: 10.1016/j.jmb.2009.04.041

Experimental method

X-RAY DIFFRACTION (1.75 Å)