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Structural analyses of PCNA from the fungal pathogen Candida albicans identify three regions with species‐specific conformations
Author(s) -
Sundaram Rajivgandhi,
Manohar Kodavati,
Patel Shraddheya Kumar,
Acharya Narottam,
Vasudevan Dileep
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14055
Subject(s) - proliferating cell nuclear antigen , biology , saccharomyces cerevisiae , dna replication , candida albicans , multiprotein complex , replication factor c , yeast , protein data bank (rcsb pdb) , microbiology and biotechnology , biochemistry , dna , genetics , eukaryotic dna replication , gene
An assembly of multiprotein complexes achieves chromosomal DNA replication at the replication fork. In eukaryotes, proliferating cell nuclear antigen (PCNA) plays a vital role in the assembly of multiprotein complexes at the replication fork and is essential for cell viability. PCNA from several organisms, including Saccharomyces cerevisiae , has been structurally characterised. However, the structural analyses of PCNA from fungal pathogens are limited. Recently, we have reported that PCNA from the opportunistic fungal pathogen Candida albicans complements the essential functions of ScPCNA in S. cerevisiae . Still, it only partially rescues the loss of ScPCNA when the yeast cells are under genotoxic stress. To understand this further, herein, we have determined the crystal structure of CaPCNA and compared that with the existing structures of other fungal and human PCNA. Our comparative structural and in‐solution small‐angle X‐ray scattering (SAXS) analyses reveal that CaPCNA forms a stable homotrimer, both in crystal and in solution. It displays noticeable structural alterations in the oligomerisation interface, P‐loop and hydrophobic pocket regions, suggesting its differential function in a heterologous system and avenues for developing specific therapeutics. Databases The PDB and SASBDB accession codes for CaPCNA are 7BUP and SASDHQ9, respectively.