Biomedical subjects

Stephen A McMahon

Publications and source records attributed to Stephen A McMahon.

3 recordsLinked to original sources

PubMed2006

Overexpression, purification, crystallization and data collection of Sulfolobus solfataricus Sso6206, a novel highly conserved protein.

Sso6206, a 10.5 kDa protein from Sulfolobus solfataricus, has been overexpressed, purified and crystallized. The protein crystallizes in space group P6(1/5)22, with unit-cell parameters a = b = 157.8, c = 307.3 A. The crystals are hexagonal bipyramids and a data set has been collected to 2.4 A resolution. Molecular replacement cannot be attempted as no convincing model can be identified. Crystals of selenomethionine-variant protein have not yet been obtained. Interestingly, crystal packing, gel filtration and mass spectrometry all suggest the native protein forms a multi-subunit oligomer consisting of >9 subunits.

Amino Acid Sequence↗

PubMed2006

Identification of a bacterial type III effector family with G protein mimicry functions.

Many bacterial pathogens use the type III secretion system to inject "effector" proteins into host cells. Here, we report the identification of a 24 member effector protein family found in pathogens including Salmonella, Shigella, and enteropathogenic E. coli. Members of this family subvert host cell function by mimicking the signaling properties of Ras-like GTPases. The effector IpgB2 stimulates cellular responses analogous to GTP-active RhoA, whereas IpgB1 and Map function as the active forms of Rac1 and Cdc42, respectively. These effectors do not bind guanine nucleotides or have sequences corresponding the conserved GTPase domain, suggesting that they are functional but not structural mimics. However, several of these effectors harbor intracellular targeting sequences that contribute to their signaling specificities. The activities of IpgB2, IpgB1, and Map are dependent on an invariant WxxxE motif found in numerous effectors leading to the speculation that they all function by a similar molecular mechanism.

Amino Acid Motifs↗

PubMed2005

The C-type lectin fold as an evolutionary solution for massive sequence variation.

Only few instances are known of protein folds that tolerate massive sequence variation for the sake of binding diversity. The most extensively characterized is the immunoglobulin fold. We now add to this the C-type lectin (CLec) fold, as found in the major tropism determinant (Mtd), a retroelement-encoded receptor-binding protein of Bordetella bacteriophage. Variation in Mtd, with its approximately 10(13) possible sequences, enables phage adaptation to Bordetella spp. Mtd is an intertwined, pyramid-shaped trimer, with variable residues organized by its CLec fold into discrete receptor-binding sites. The CLec fold provides a highly static scaffold for combinatorial display of variable residues, probably reflecting a different evolutionary solution for balancing diversity against stability from that in the immunoglobulin fold. Mtd variants are biased toward the receptor pertactin, and there is evidence that the CLec fold is used broadly for sequence variation by related retroelements.

Amino Acid Sequence↗