A peptide from the adenovirus fiber shaft forms amyloid‐type fibrils

Abstract

The fiber protein of adenovirus consists of a Cterminal globular head, a shaft and a short N-terminal tail. The crystal structure of a stable domain comprising the head plus a part of the shaft of human adenovirus type 2 fiber has recently been solved at 2.4 A î resolution Nature 401, 935^938]. A peptide corresponding to the portion of the shaft immediately adjacent to the head (residues 355^396) has been synthesized chemically. The peptide failed to assemble correctly and instead formed amyloid-type fibrils as assessed by electron microscopy, Congo red binding and X-ray diffraction. Peptides corresponding to the fiber shaft could provide a model system to study mechanisms of amyloid fibril formation.z 2000 Federation of European Biochemical Societies.

Amyloid Fibril Formation from Sequences of a Natural β-Structured Fibrous Protein, the Adenovirus Fiber

“…C-terminal amide derivatives of the peptides were synthesized by the stepwise solid phase method using an Applied Biosystems 430A automated synthesizer as described previously (25). The 41-, 25-, 12-, and 4-amino acid peptides as well as the GAIPIG peptide were synthesized in-house; the 8-and 6-amino acid peptides were obtained from Bachem, France.…”

“…Lower panel, structure of the peptides within the native shaft segment (adapted from Ref. 25). One of the strands of the trimeric shaft is shown in black and the other two in gray.…”

“…Given their repetitive nature, we have proposed previously (25) that these sequences need to be brought into a correct register in order to assemble into the triple ␤-spiral. This registration role can be played either by the native globular head or by a foreign trimerization motif as we have shown recently (24),.…”

“…As part of this study, we initially synthesized a 41-amino acid peptide (PIKTKIGSGIDYNENGAMITKLGSGLSFDNSGAITIGNKND) corresponding to the shaft sequence that is immediately adjacent to the head. This peptide failed to assemble into the triple ␤-spiral conformation observed in the single crystal study of the stable domain; instead, it aggregated into fibrils similar to those associated with amyloid diseases, namely long, unbranched structures that stain with the dye Congo Red and give a characteristic x-ray fiber diffraction pattern (25). Given these observations, it seems that amino acid sequences from the adenovirus shaft may also provide a simple and well defined model system for the study of amyloid.…”

“…Furthermore, we have synthesized and studied a variant of the 6-amino acid peptide where the central threonine has been replaced by proline (GAIPIG). We also include infrared studies and synchrotron x-ray diffraction patterns of the 41-aa 1 peptide that were not available at the time the original paper was published (25). We find that amyloid formation is a general tendency of the shaft sequences in the absence of the globular head, and we discuss the results in the context of the native fiber folding and assembly.…”