species are ubiquitous fungal commensals that are present in ~80% of the human population. However, impairment of host immunity or the normal host microbiota can lead to Candida
overgrowth and disease. As a result, Candida
spp. are also the most frequent cause of opportunistic mycoses worldwide. Skin and oral Candida
infections are common in HIV-positive individuals (Gaitán-Cepeda et al.
) and vaginal candidiasis is frequent in normally healthy women (Sobel et al.
). Risk factors for severe systemic candidiasis include immunosuppression, either through disease or immunotherapy (such as that associated with organ transplantation), or the use of medical implants. C. albicans
and other Candida
spp. have emerged as the sixth most frequently isolated pathogen in hospitals (Jarvis, 1995
; Pfaller & Diekema, 2007
) and the fourth most frequent cause of nosocomial bloodstream infections, with a mortality rate of up to 50% when these develop into severe systemic forms (Gudlaugsson et al.
Adherence to host cells is one of the major determinants of Candida
pathogenesis and a key step in the infection process. The agglutinin-like sequence (Als) family of surface proteins (Als1–7 and Als9) has been implicated in the adhesion of C. albicans
to host cells and in binding to a broad range of proteins in cell surfaces and the extracellular matrix (Gaur & Klotz, 1997
; Phan et al.
). Moreover, Als1 and Als5 have been shown to bind a large variety of sequences from a library of random heptameric peptides (Klotz et al.
). Structural studies are essential for the understanding of the mechanism that allows the association of Als proteins with such a diverse variety of ligands and its implication in the infection process.
The Als adhesins are composed of four distinct protein regions: a poorly glycosylated N-terminal region of approximately 320 amino acids, with 41–84% similarity among Als members, and a nonrepeat Thr-rich region of 103 amino acids followed by two highly glycosylated regions: a central Thr-rich domain with a variable number of 36-amino-acid repeats and a Ser/Thr/Asn-rich membrane-anchoring C-terminal domain of variable length (Hoyer, 2001
). The N-terminal region, in which the observed cell-adhesion properties have been shown to reside (Sheppard et al.
; Loza et al.
), is predicted to form a predominant β-structure.
In order to describe in atomic detail the mode of peptide binding and the conformational changes that occur upon the transition from free protein to protein–ligand complex, we used protein X-ray crystallography and nuclear magnetic resonance (NMR). Our preliminary NMR data from the N-terminal domain of Als revealed an IgG-superfamily secondary-structure topology (Yan et al.
). Here, we report the expression, crystallization and preliminary X-ray data analysis of the N-terminal region of one member of the Als family: NT-Als9-2.