Characterization of the sialic acid-binding site in sialoadhesin by site-directed mutagenesis. by Vinson, M, van der Merwe, P, Kelm, S, May, A, Jones, E, Crocker, P

“…Here we have carried out site-directed mutagenesis in an attempt to identify the binding site of sialoadhesin. …”

A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse. by Isaacs, A, Oliver, P, Jones, E, Jeans, A, Potter, A, Hovik, B, Nolan, P, Vizor, L, Glenister, P, Simon, A, Gray, I, Spurr, N, Brown, S, Hunter, A, Davies, K

“…The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. …”

A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse by Isaacs, A, Oliver, P, Jones, E, Jeans, A, Potter, A, Hovik, B, Nolan, P, Vizor, L, Glenister, P, Simon, A, Gray, I, Spurr, N, Brown, S, Hunter, A, Davies, K

“…The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. …”

The structure of tumour necrosis factor--implications for biological function. by Jones, E, Stuart, D, Walker, N

“…Published data on site-directed mutagenesis and antibody binding may now be assessed in the light of the structure, thus the links between structure and function for TNF may be addressed. …”

Crystal structure of a heparin- and integrin-binding segment of human fibronectin. by Sharma, A, Askari, J, Humphries, M, Jones, E, Stuart, D

“…Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for alpha4beta1 binding to FN12-14. …”

A dual binding mode for RhoGTPases in plexin signalling by Bell, C, Aricescu, A, Jones, E, Siebold, C

“…On inclusion of the juxtamembrane helix, a trimeric structure of Plexin-B1-Rac1 complexes is stabilised by a second, novel, RhoGTPase binding site adjacent to the Ras site. Site-directed mutagenesis combined with cellular and biophysical assays demonstrate that this new binding site is essential for signalling. …”

The crystal structure of murine leukemia inhibitory factor by Robinson, R, Grey, L, Staunton, D, Stuart, D, Heath, J, Jones, E

“…Analysis of published mutagenesis data implicate two regions of receptor interaction which are located in the fourth helix and the preceding loop. …”

Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP. by Bishop, B, Aricescu, A, Harlos, K, O'Callaghan, C, Jones, E, Siebold, C

“…The interaction determinants, confirmed by biophysical studies and mutagenesis, reveal previously uncharacterized and distinct functions for the Hh Zn2+ and Ca2+ binding sites--functions that may be common to all vertebrate Hh proteins. …”

Structure and functional analysis of the IGF-II/IGF2R interaction. by Brown, J, Delaine, C, Zaccheo, O, Siebold, C, Gilbert, R, van Boxel, G, Denley, A, Wallace, J, Hassan, A, Forbes, B, Jones, E

“…Our complex shows that Phe19 and Leu53 of IGF-II lock into a hydrophobic pocket unique to domain 11 of mammalian IGF2Rs. Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding proteins and IGF2R have converged on the same high-affinity site.…”

A dual binding mode for RhoGTPases in plexin signalling by Bell, C, Aricescu, A, Jones, E, Siebold, C

“…On inclusion of the juxtamembrane helix, a trimeric structure of Plexin-B1-Rac1 complexes is stabilised by a second, novel, RhoGTPase binding site adjacent to the Ras site. Site-directed mutagenesis combined with cellular and biophysical assays demonstrate that this new binding site is essential for signalling. …”

The crystal structure of murine leukemia inhibitory factor. by Robinson, R, Grey, L, Staunton, D, Stuart, D, Heath, J, Jones, E

“…Analysis of published mutagenesis data implicate two regions of receptor interaction which are located in the fourth helix and the preceding loop. …”

Interactions of IGF-II with the IGF2R/cation-independent mannose-6-phosphate receptor mechanism and biological outcomes. by Brown, J, Jones, E, Forbes, B

“…This review highlights recent advances in understanding the IGF2R structure and mechanism of interaction with its ligands, in particular IGF-II. Recent mutagenesis studies combined with the crystal structure of domains 11-14 in complex with IGF-II have mapped the sites of interaction and explain how the IGF2R specificity for IGF-II is achieved. …”

Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. by Aricescu, A, Hon, W, Siebold, C, Lu, W, Van Der Merwe, P, Jones, E

“…Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. …”

Sialic acid recognition by sialoadhesin and related lectins by Vinson, M, Mucklow, S, May, A, Jones, E, Kelm, S, Crocker, P

“…By generating truncated recombinant proteins, together with site-directed mutagenesis, the GFCC'C" faces of the NH2-terminal V-set domains of sialoadhesin and CD22 have been shown to contain the sialic acid binding site. …”

Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding by Walters, L, Harlos, K, Brackenridge, S, Rozbesky, D, Barrett, J, Jain, V, Walter, T, O'Callaghan, C, Borrow, P, Toebes, M, Hansen, S, Sacha, J, Abdulhaqq, S, Greene, J, Früh, K, Marshall, E, Picker, L, Jones, E, McMichael, A, Gillespie, G

“…Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. …”

Identification of a di-leucine motif within the C terminus domain of the Menkes disease protein that mediates endocytosis from the plasma membrane. by Francis, M, Jones, E, Levy, E, Martin, R, Ponnambalam, S, Monaco, A

“…Further studies were performed on putative internalisation motifs, using site-directed mutagenesis, protein expression, chemical treatment and immunofluorescence. …”

Computational model for the IGF-II/IGF2r complex that is predictive of mutational and surface plasmon resonance data. by Roche, P, Brown, J, Denley, A, Forbes, B, Wallace, J, Jones, E, Esnouf, R

“…These plausible complexes were then critically assessed using an array of analysis techniques including consideration of additional mutagenesis data. One model was strongly supported by these analyses and is discussed here in detail. …”

Crystal structure and functional dissection of the cytostatic cytokine oncostatin M. by Deller, M, Hudson, K, Ikemizu, S, Bravo, J, Jones, E, Heath, J

“…RESULTS: We report here the crystal structure of human oncostatin M (hOSM) along with mutagenesis data which map the receptor-binding epitopes of the molecule. …”

A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin-biased signaling by Gorvin, C, Babinsky, V, Malinauskas, T, Nissen, P, Schou, A, Hanyaloglu, A, Siebold, C, Jones, E, Hannan, F, Thakker, R

“…Homology modeling and mutagenesis studies showed that the R680G CaSR mutation selectively enhanced β-arrestin signaling by disrupting a salt bridge formed between Arg680 and Glu767, which are located in CaSR transmembrane domain 3 and extracellular loop 2, respectively. …”

Classical and nonclassical class I major histocompatibility complex molecules exhibit subtle conformational differences that affect binding to CD8alphaalpha. by Gao, G, Willcox, B, Wyer, JR, Boulter, J, O'Callaghan, C, Maenaka, K, Stuart, D, Jones, E, Van Der Merwe, P, Bell, J, Jakobsen, B

“…Interestingly, CD8alphaalpha bound normally to the nonclassical MHC molecule HLA-G (K(d) approximately 150 microm), but only weakly to the natural killer cell receptor ligand HLA-E (K(d) >/= 1 mm). Site-directed mutagenesis experiments revealed that variation in CD8alphaalpha binding affinity can be explained by amino acid differences within the alpha3 domain. …”