title: Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms.
abstract: Staphylococcal bacteria, including Staphylococcus epidermidis and Staphylococcus aureus, cause chronic biofilm-related infections. The homologous proteins Aap and SasG mediate biofilm formation in S. epidermidis and S. aureus, respectively. The self-association of these proteins in the presence of Zn(2+) leads to the formation of extensive adhesive contacts between cells. This study reports the crystal structure of a Zn(2+) -bound construct from the self-associating region of Aap. Several unusual structural features include elongated β-sheets that are solvent-exposed on both faces and the lack of a canonical hydrophobic core. Zn(2+)-dependent dimers are observed in three distinct crystal forms, formed via pleomorphic coordination of Zn(2+) in trans across the dimer interface. These structures illustrate how a long, flexible surface protein is able to form tight intercellular adhesion sites under adverse environmental conditions.
authors.affiliation: Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Conrady
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Herr
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D018441:Biofilms / Q000254:growth & development*; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013210:Staphylococcus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D055672:Static Electricity; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; D011994:Recombinant Proteins; C524374:SasG protein, Staphylococcus aureus; D015032:Zinc