Structure of human Vitronectin C-terminal domain and interaction with Yersinia pestis outer membrane protein Ail

Sci Adv. 2019 Sep 11;5(9):eaax5068. doi: 10.1126/sciadv.aax5068. eCollection 2019 Sep.


Vitronectin (Vn) is a major component of blood that controls many processes central to human biology. It is a drug target and a key factor in cell and tissue engineering applications, but despite long-standing efforts, little is known about the molecular basis for its functions. Here, we define the domain organization of Vn, report the crystal structure of its carboxyl-terminal domain, and show that it harbors the binding site for the Yersinia pestis outer membrane protein Ail, which recruits Vn to the bacterial cell surface to evade human host defenses. Vn forms a single four-bladed β/α-propeller that serves as a hub for multiple functions. The structure explains key features of native Vn and provides a blueprint for understanding and targeting this essential human protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Protein Binding
  • Protein Conformation
  • Sequence Homology
  • Virulence Factors / chemistry
  • Virulence Factors / metabolism*
  • Vitronectin / chemistry
  • Vitronectin / metabolism*
  • Yersinia pestis / metabolism*


  • Ail protein, Yersinia pestis
  • Bacterial Outer Membrane Proteins
  • Virulence Factors
  • Vitronectin