Protein tentacles

Abstract

Virus structures were among the earliest illustrations of how regulated protein assembly can proceed by folding of polypeptide-chain segments into complementary sites on partner proteins. I draw on Caspar's image of protein "tentacles" and his metaphor of SV40 pentamers as five-legged, aquatic organisms ("pentopuses") to suggest a helpful vocabulary. "Tentacular interactions" among component subunits organize most subcellular molecular machines. Their selective advantages include facile regulation of both assembly and disassembly by modifying enzymes and by folding chaperones.

Keywords: Peptide-surface association; Protein interactions; Regulated assembly; Virus structure.

Fig. 1

TBSV. The 180-subunit (T=3) shell assembles from dimers of a 40 kDa protein subunit (bottom). Subunits at the three quasi-equivalent positions in the capsid, designated A, B and C, cluster as 60 A:B dimers and 30 C:C dimers. The A and B conformations are nearly identical, but differ from the C conformation by the hinge angle between the two globular domains ("shell", S, and "projection", P) and unfolding of the arm (middle). The positively charged, 66-residue R segment at the N-terminus interacts with the viral RNA; segments on subunits that nucleate assembly may co-fold with RNA packaging signals. The folded arms of C:C dimers interact with arms from two other C:C dimers, creating an inner scaffold (top right). The C:C contact (and the C:B contact) along one side of the A:B:C triangle is "divided" by the scaffold of arms; the A:B contact (and the A:A contact) along the two other sides of the A:B:C triangle is "direct" (top left). The interaction between S domains in the two dimers is essentially a rotation around a fixed fulcrum, conserving many of the side-chain contacts; the P-domain contacts are invariant.

Fig. 2

SV40 and murine polyoma virus. The 72 VP1 pentamers (top right) interact with each other almost exclusively through their C-terminal "tentacles", projecting from a pentamer of jelly-roll β-barrel domains (top left). The tentacles insert into "slots" in neighboring pentamers. Disulfide bonds and divalent cation bridges then lock the tentacles in place (top right). Bottom: Don Caspar's representation: a pentopus (left) and its "frozen embrace" with neighbors (right). (From (Caspar, 1992))