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Review
. 2024 Dec;125(12):e30406.
doi: 10.1002/jcb.30406. Epub 2023 Apr 23.

Structure and function of the TPR-domain immunophilins FKBP51 and FKBP52 in normal physiology and disease

Olga B Soto  1 , Christian S Ramirez  1 , Rina Koyani  1 , Isela A Rodriguez-Palomares  1 , Jessica R Dirmeyer  1 , Brian Grajeda  1 , Sourav Roy  1 , Marc B Cox  1   2
Affiliations
Review

Structure and function of the TPR-domain immunophilins FKBP51 and FKBP52 in normal physiology and disease

Olga B Soto et al. J Cell Biochem. 2024 Dec.

Abstract

Coordinated cochaperone interactions with Hsp90 and associated client proteins are crucial for a multitude of signaling pathways in normal physiology, as well as in disease settings. Research on the molecular mechanisms regulated by the Hsp90 multiprotein complexes has demonstrated increasingly diverse roles for cochaperones throughout Hsp90-regulated signaling pathways. Thus, the Hsp90-associated cochaperones have emerged as attractive therapeutic targets in a wide variety of disease settings. The tetratricopeptide repeat (TPR)-domain immunophilins FKBP51 and FKBP52 are of special interest among the Hsp90-associated cochaperones given their Hsp90 client protein specificity, ubiquitous expression across tissues, and their increasingly important roles in neuronal signaling, intracellular calcium release, peptide bond isomerization, viral replication, steroid hormone receptor function, and cell proliferation to name a few. This review summarizes the current knowledge of the structure and molecular functions of TPR-domain immunophilins FKBP51 and FKBP52, recent findings implicating these immunophilins in disease, and the therapeutic potential of targeting FKBP51 and FKBP52 for the treatment of disease.

Keywords: FKBP51; FKBP52; immunophilin.

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