TY - JOUR
T1 - Structural insights into ail-mediated adhesion in Yersinia pestis
AU - Yamashita, Satoshi
AU - Lukacik, Petra
AU - Barnard, Travis J.
AU - Noinaj, Nicholas
AU - Felek, Suleyman
AU - Tsang, Tiffany M.
AU - Krukonis, Eric S.
AU - Hinnebusch, B. Joseph
AU - Buchanan, Susan K.
N1 - Funding Information:
The authors thank N. Suzuki for providing samples, technical support, and discussions, and H. Bernstein and J. Fairman for reading the manuscript. S.Y., P.L., T.J.B., N.N., and S.K.B. are supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. B.J.H. is supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. S.F., T.M.T., and E.S.K. are supported by NIH Grant R21AI090194 to E.S.K. Data were collected at Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-ID at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at http://www.ser-cat.org/members.html . Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.
PY - 2011/11/9
Y1 - 2011/11/9
N2 - Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells.
AB - Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells.
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U2 - 10.1016/j.str.2011.08.010
DO - 10.1016/j.str.2011.08.010
M3 - Article
C2 - 22078566
AN - SCOPUS:80855144811
VL - 19
SP - 1672
EP - 1682
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 11
ER -
