Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A. by Williams, P, Chaudhry, Y, Goodfellow, I, Billington, J, Powell, R, Spiller, O, Evans, D, Lea, S

“…We describe the x-ray structure of a pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the three domains required for regulation of human complement. We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55.…”

Further structural insights into the binding of complement factor H by complement regulator-acquiring surface protein 1 (CspA) of Borrelia burgdorferi. by Caesar, J, Wallich, R, Kraiczy, P, Zipfel, P, Lea, S

“…Acquisition is mediated by a family of complement regulator-acquiring surface proteins (CRASPs), of which the atomic structure of CspA (BbCRASP-1) is known and shows the formation of a homodimeric species which is required for binding. Mutagenesis studies have mapped a putative factor H binding site to a cleft between the two subunits. …”

Molecular model of a type III secretion system needle: Implications for host-cell sensing. by Deane, J, Roversi, P, Cordes, F, Johnson, S, Kenjale, R, Daniell, S, Booy, F, Picking, W, Picking, W, Blocker, A, Lea, S

“…The model, combined with mutagenesis data, reveals that signaling of host-cell contact is relayed through the needle via intersubunit contacts and suggests a mode of binding for a tip complex.…”

Structural basis for complement factor H linked age-related macular degeneration. by Prosser, B, Johnson, S, Roversi, P, Herbert, A, Blaum, B, Tyrrell, J, Jowitt, T, Clark, S, Tarelli, E, Uhrín, D, Barlow, P, Sim, R, Day, A, Lea, S

“…This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance-monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG-FH complex.…”

Structural analysis uncovers lipid-binding properties of Notch ligands. by Chillakuri, C, Sheppard, D, Ilagan, M, Holt, L, Abbott, F, Liang, S, Kopan, R, Handford, P, Lea, S

“…Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. …”

The substrate specificity switch FlhB assembles onto the export gate to regulate type three secretion by Kuhlen, L, Johnson, S, Andreas Zeitler, Baurle, S, Deme, J, Caesar, J, Debo, R, Fisher, J, Wagner, S, Lea, S

“…Structure-informed mutagenesis suggests that this loop is critical in gating secretion and we propose that a series of conformational changes in the T3SS trigger opening of the gate through interactions between FlhB/SctU and FliPQR/SctRST. …”

Structural and Functional Studies on the N-terminal Domain of the Shigella Type III Secretion Protein MxiG by McDowell, M, Johnson, S, Deane, J, Cheung, M, Roehrich, A, Blocker, A, McDonnell, J, Lea, S

“…However, the putative phosphate-binding pocket of MxiG-N(6-112) does not align with other FHA domain structures or interact with Thr(P). Furthermore, mutagenesis of potential phosphate-binding residues has no effect on S. flexneri T3SS assembly and function. …”

Structural and functional studies on the N-terminal domain of the Shigella type III secretion protein MxiG. by McDowell, M, Johnson, S, Deane, J, Cheung, M, Roehrich, A, Blocker, A, McDonnell, J, Lea, S

“…However, the putative phosphate-binding pocket of MxiG-N(6-112) does not align with other FHA domain structures or interact with Thr(P). Furthermore, mutagenesis of potential phosphate-binding residues has no effect on S. flexneri T3SS assembly and function. …”

Hydrophilic domain II of Escherichia coli Dr fimbriae facilitates cell invasion. by Das, M, Hart-Van Tassell, A, Urvil, P, Lea, S, Pettigrew, D, Anderson, K, Samet, A, Kur, J, Matthews, S, Nowicki, S, Popov, V, Goluszko, P, Nowicki, B

“…We used alanine scanning mutagenesis to replace selected amino acids in hydrophilic domain II of the structural fimbrial subunit DraE and evaluated recombinant mutant DraE for attachment, invasion, and intracellular compartmentalization. …”

Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H. by Kraiczy, P, Hanssen-Hübner, C, Kitiratschky, V, Brenner, C, Besier, S, Brade, V, Simon, M, Skerka, C, Roversi, P, Lea, S, Stevenson, B, Wallich, R, Zipfel, P

“…Based on the crystallographic structure an in vitro mutagenesis approach was conducted to identify amino acid residues which are relevant for FHL-1 and factor H binding by exchanging single or multiple residues in region 1 and the C-terminally located region 3. …”

Structural and functional characterisation of properdin and properdin-binding complement inhibitors from ticks by Ahn, J

“…The structures of these inhibitors, in combination with mutagenesis studies of CIRp-A1, suggested that a loop contributes to the inhibitory activity of CIRp-A1.…”