A Glimpse Into the Structure and Function of Atypical Type I Chaperonins

Abstract

Chaperonins are a subclass of molecular chaperones that assist cellular proteins to fold and assemble into their native shape. Much work has been done on Type I chaperonins, which has elucidated their elegant mechanism. Some debate remains about the details in these mechanisms, but nonetheless the roles of these in helping protein folding have been understood in great depth. In this review we discuss the known functions of atypical Type I chaperonins, highlighting evolutionary aspects that might lead chaperonins to perform alternate functions.

Keywords: GroEL; GroES; Mycobacterium tuberculosis; Type I chaperonins; gene duplication; protein folding.

Figure 1

Structural features of the Type I, Type II, and Type III chaperonins. The comparative structure analysis of Type I, Type II, and Type III chaperonins. Structures were downloaded from the RCSB with codes of PDB: 1AON, 3RUW, and 5X9U, respectively. Type I chaperonin is demarcated into Apical, Intermediate, and Equatorial domains, analogous regions of which are shown in Type II and III chaperonins using dotted lines. Type II chaperonin has a characteristic built-in lid in the structure that plays the role of co-chaperonin GroES of Type I chaperonin. Type III chaperonins are structurally similar to Type II chaperonins in having built-in-lid. However, the sequence, structure and function of the lid are distinct in Type II and Type III chaperonins (An et al., 2017). The PyMOL program (PyMOL Molecular Graphics System, version 1.3) was used to generate this figure.

Figure 2

The crystal structure of M. tuberculosis GroEL2 superimposed on E. coli GroEL-ES structure. The structure of M. tuberculosis GroEL2 (PDB ID:1SJP) shows lower oligomeric status (dimer). Colored in blue, green, and red are the Apical, Intermediate and Equatorial domain, respectively. Compared to E. coli GroEL (PDB ID: 1AON) shown in gray color, the inter-subunit interaction is mediated through Apical domain in M. tuberculosis GroEL2 structure whereas inter-subunit interaction is through Equatorial domain in E. coli GroEL. Single subunit of M. tuberculosis GroEL2 is aligned to E. coli GroES bound GroEL ring representing asymmetric model. GroES structure has been removed for simplicity. A single subunit of E. coli GroEL has been shown with the same color-coded domains compared to M. tuberculosis GroEL2 for comparative analysis. The PyMOL program (PyMOL Molecular Graphics System, version 1.3) was used to generate this figure.

Figure 3

Multiple chaperonins in bacteria displaying diversity at C-terminal. Sequence alignment highlighting C-terminal regions of the representative bacterial GroEL homologs with the E. coli GroEL. The last C-terminal residues of selected multiple GroELs in different bacteria show divergence from the canonical (GGM)4M motif of the E. coli GroEL shown in dotted red box. Sequences were retrieved from www.uniprot.org and aligned in MEGA6 using MUSCLE algorithm (www.megasoftware.net). Formatting of aligned sequences were done in Jalview alignment viewer (www.jalview.org). Residues in the alignment follow the default Clustal color scheme of Jalview.