Actin-based motility of the intracellular pathogen Listeria monocytogenes: assessing the inhibitory specificity of ABM-1 peptide analogues.
Actin-Based Motility motifs [ABM-1 sequence = (D/E)FPPPPX(D/E), where X = P or T, and ABM-2 sequence = XPPPPP, where X denotes G, A, L, P, and S] facilitate assembly of an activated motility complex. Potent inhibition of intracellular motility of pathogens by ABM-1 and ABM-2 peptide analogues has served as a criterion for investigating actin-based motility. To assess the specificity of ABM-1 peptide inhibitors, we microinjected proline-rich peptides into Listeria-infected PtK2 host cells. Use of a combinatorial ABM-1 peptide library (empirical formula = D1E2F2P4T1) demonstrated that high-potency inhibition requires a precise sequence, and not merely a particular amino acid composition. Calculated concentrations of specific sequences in this library indicate that the entire (D/E)FPPPPX(D/E) motif is needed to achieve high-affinity inhibition in living cells. The failure of the well known proline-rich SH3 binding antagonists VSL-12 or APP-12 to inhibit Listeria motility also indicates that SH3 interactions are unlikely to control actin-based motility directly.
Purich
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DL
Department of Biochemistry & Molecular Biology, University of Florida College of Medicine, Health Science Center, Gainesville 32610-0245, USA. dlpurich@biochem.med.ufl.edu
Southwick
F S
FS
D000199:Actins / Q000502:physiology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology*; D008089:Listeria monocytogenes / Q000166:cytology* / Q000502:physiology*; D010455:Peptides / Q000502:physiology
D000199:Actins; D001426:Bacterial Proteins; D010455:Peptides