9n4d

Cryo-EM structure of Candida albicans pH regulated antigen 1 (Pra1) protein in complex with Zn2+

spinqualitylabelsall models 9n4d, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9n4d is a 6 chain structure with sequence from Candida albicans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRA1_CANAL Cell surface protein involved in the host-parasite interaction during candidal infection (PubMed:17277107, PubMed:19850343, PubMed:20504767, PubMed:20644161, PubMed:21212281, PubMed:21245270, PubMed:21820180, PubMed:22074954, PubMed:22761575, PubMed:22844116, PubMed:9440517). With MP65, represents a major component of the biofilm matrix (PubMed:17277107). As a surface protein, binds the two human complement regulators CFH and CFHR1, as well as plasminogen PLG, mediates complement evasion and extra-cellular matrix interaction and/or degradation (PubMed:19850343, PubMed:20504767). As a released protein, enhances complement control in direct vicinity of the yeast and thus generates an additional protective layer which controls host complement attack, assisting the fungus in escaping host surveillance (PubMed:17277107, PubMed:19850343). Binds to host fluid-phase C3 and blocks cleavage of C3 to C3a and C3b, leading to inhibition of complement activation and protection from uptake of C.albicans by human macrophages (PubMed:20644161). Also mediates human complement control and complement evasion through binding to C4BPA, another human complement inhibitor, as well as through binding to host integrin alpha-M/beta-2 (PubMed:21212281, PubMed:21245270, PubMed:21820180, PubMed:22844116). Binds zinc from its environment and then reassociates with ZRT1 to acquire this essential metal (PubMed:22761575). Publication Abstract from PubMed Candida albicans causes over 400,000 life-threatening, and an additional half a billion of mucosal infections annually. In response to infection, the host limits essential micronutrient availability, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential for C. albicans pathogenicity, limitation induces secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is unknown. Here, we present cryo-EM structures of C. albicans Pra1 in apo- and zinc-bound states, at 2.8 and 2.5 A resolution respectively. Our work reveals a hexameric ring with multiple zinc binding sites. Through genetic studies, we show that these sites are essential for C. albicans growth under zinc restriction but do not affect the inflammatory properties of Pra1. These data create a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions, C. albicans zinc uptake, as well as therapeutics development. Structural insights into mechanisms of zinc scavenging by the Candida albicans zincophore Pra1.,Nore A, Roselletti E, Chakraborty T, Sarkka N, Perera RL, Wilson D, Syrjanen JL Nat Commun. 2025 Nov 28;16(1):10753. doi: 10.1038/s41467-025-65782-0. PMID:41315346 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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