6QP4

Structure of 299-452 fragment of the UspA1 protein from Moraxella catarrhalis

Summary for 6QP4

• Entry DOI: 10.2210/pdb6qp4/pdb
• Descriptor: UspA1, CHLORIDE ION, HEXANE-1,6-DIOL, ... (5 entities in total)
• Functional Keywords: moraxella catarrhalis, uspa1, trimeric autotransporter, c3d protein binding, cell adhesion
• Biological source: Moraxella catarrhalis (Branhamella catarrhalis)
• Total number of polymer chains: 3
• Total formula weight: 52827.82

Authors

Mikula, K.M.,Kolodziejczyk, R.,Goldman, A. (deposition date: 2019-02-13, release date: 2019-08-21, Last modification date: 2024-01-24)

Primary citation

Mikula, K.M.,Kolodziejczyk, R.,Goldman, A.
Structure of the UspA1 protein fragment from Moraxella catarrhalis responsible for C3d binding.
J.Struct.Biol., 208:77-85, 2019

PubMed Abstract: The gram-negative bacterium Moraxella catarrhalis infects humans exclusively, causing various respiratory tract diseases, including acute otitis media in children, septicaemia or meningitis in adults, and pneumonia in the elderly. To do so, M. catarrhalis expresses virulence factors facilitating its entry and survival in the host. Among them are the ubiquitous surface proteins (Usps): A1, A2, and A2H, which all belong to the trimeric autotransporter adhesin family. They bind extracellular matrix molecules and inhibit the classical and alternative pathways of the complement cascade by recruiting complement regulators C3d and C4b binding protein. Here, we report the 2.5 Å resolution X-ray structure of UspA1, which previous work had suggested contained the canonical C3d binding site found in both UspA1 and UspA2. We show that this fragment of the passenger domain contains part of the long neck domain (residues 299-336) and a fragment of the stalk (residues 337-452). The coiled-coil stalk is left-handed, with 7 polar residues from each chain facing the core and coordinating chloride ions or water molecules. Despite the previous reports of tight binding in serum-based assays, we were not able to demonstrate binding between C3d and UspA1 using ELISA or biolayer interferometry, and the two proteins run separately on size-exclusion chromatography. Microscale thermophoresis suggested that the dissociation constant was 140.5 ± 8.4 μM. We therefore suggest that full-length proteins or other additional factors are important in UspA1-C3d interactions. Other molecules on the bacterial surface or present in serum may enhance binding of those two molecules.

PubMed: 31400508
DOI: 10.1016/j.jsb.2019.08.002

Experimental method

X-RAY DIFFRACTION (2.5 Å)