Symmetry, stability, and dynamics of multidomain and multicomponent protein systems

Abstract

Symmetry is commonly observed in many biological systems. Here we discuss representative examples of the role of symmetry in structural molecular biology. Point group symmetries are observed in many protein oligomers whose three-dimensional atomic structures have been elucidated by x-ray crystallography. Approximate symmetry also occurs in multidomain proteins. Symmetry often confers stability on the molecular system and results in economical usage of basic components to build the macromolecular structure. Symmetry is also associated with cooperativity. Mild perturbation from perfect symmetry may be essential in some systems for dynamic functions.

Figure 1

Crystal structure of pentameric human serum amyloid P-component (11) showing 5-fold symmetry.

Figure 2

The structure of the zinc insulin hexamer as defined by Hodgkin and coworkers (14). The hexamer is viewed down the exact 3-fold axis (triangle at the center); the arrows indicate positions of approximate 2-fold axes relating pairs of protomers. Each protomer is represented in a specific color, and the zinc at the center is shown in red.

Figure 3

Quaternary structures of proteins with the lectin fold. The crystal structures used are pea lectin (32), bovine S-lectin (33), peanut lectin (34), jack bean concanavalin A (35), and human serum amyloid P-component (11). The hexameric Limulus C-reactive protein (Limulus CRP) structure has been generated on the basis of sequence similarity with serum amyloid P-component (36). Symmetry axes are indicated for each structure. Arrows represent 2-fold axes in the plane of the paper.

Figure 4

Internal symmetry in γ_B-crystallin (45, 46). The two symmetry-related Greek-key motifs within a domain are shown in two different colors and are related by approximate 2-fold axes (arrows). In a similar manner, the two domains are related by an approximate 2-fold axis.

Figure 5

(a and b) Comparison of monomeric pepsin (a) with two symmetry-related lobes (61) and dimeric HIV proteinase (b) (4) inspired by the analyses of Blundell and coworkers (–63). The arrows indicate the positions of approximate and perfect 2-fold axes relating domains (pepsin) and protomers (HIV proteinase), respectively. (c) The two topologically equivalent catalytic groups (the “hands” Asp-32 and Asp-215 of pepsin), which have an approximate 2-fold axis shown as an arrow.

Figure 5

(a and b) Comparison of monomeric pepsin (a) with two symmetry-related lobes (61) and dimeric HIV proteinase (b) (4) inspired by the analyses of Blundell and coworkers (–63). The arrows indicate the positions of approximate and perfect 2-fold axes relating domains (pepsin) and protomers (HIV proteinase), respectively. (c) The two topologically equivalent catalytic groups (the “hands” Asp-32 and Asp-215 of pepsin), which have an approximate 2-fold axis shown as an arrow.