Structural Characteristics, Binding Partners and Related Diseases of the Calponin Homology (CH) Domain

Abstract

The calponin homology (CH) domain is one of the most common modules in various actin-binding proteins and is characterized by an α-helical fold. The CH domain plays important regulatory roles in both cytoskeletal dynamics and signaling. The CH domain is required for stability and organization of the actin cytoskeleton, calcium mobilization and activation of downstream pathways. The CH domain has recently garnered increased attention due to its importance in the onset of different diseases, such as cancers and asthma. However, many roles of the CH domain in various protein functions and corresponding diseases are still unclear. Here, we review current knowledge about the structural features, interactome and related diseases of the CH domain.

Keywords: CH-domain-containing proteins; actin cytoskeleton; calmodulin; cancer; transgelin-2; tropomyosin; tubulin; α-helix.

FIGURE 1

Structural characteristics of the CH domain. (A) Sequence alignment, schematic of the secondary structure elements and the binding sites of CH domain for actin and signaling proteins. The conserved residues among the three CH domains are colored. Schematics of the secondary structure elements of CH domain and binding sites are also included. UniProt identifiers for CH1 (α-actinin), CH2 (MICAL, Molecule interacting with CasL) and CH3 (calponin-1) are P12814, Q8TDZ2, P51911. (B) The tertiary fold of the calponin CH domain (PDB: 1H67). The CH domain contains in total six α-helices. Helices III and VI are approximately parallel, while helix IV is lying oblique aside. The structural model was generated by UCSF Chimera. Abbreviations: αPIX: Cdc42/Rac1-specific guanine nucleotide exchanging factor; CaM: calmodulin; ERK: extracellular signal-regulated kinase; MT-2: metallothionein-2; TPM: tropomyosin; TSG12: a specific transgelin-2 agonist.