Design of protein struts for self-assembling nanoconstructs

doi:10.1073/pnas.132544299

Design of protein struts for self-assembling nanoconstructs

^*NanoFrames LLC, Boston, MA 02118; ^†Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111; and ^§Department of Chemical Engineering, Tufts University, Medford, MA 02155

Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved April 29, 2002 (received for review October 12, 2001)

Abstract

Bacteriophage T4 tail fibers have a quaternary structure of bent rigid rods, 3 × 160 nm in size. The four proteins which make up these organelles are able to self-assemble in an essentially irreversible manner. To use the self-assembly domains of these proteins as elements in construction of mesoscale structures, we must be able to rearrange these domains without affecting the self-assembly properties and add internal binding sites for other functional elements. Here we present results on several alterations of the P37 component of the T4 tail fiber that change its length and add novel protein sequences into the protein. One of these sequences is an antibody binding site that is used to inactivate phage carrying the modified gene.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: phyman{at}nanoframes.com
This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Nanoscience: Underlying Physical Concepts and Phenomena,” held May 18–20, 2001, at the National Academy of Sciences in Washington, DC.
This paper was submitted directly (Track II) to the PNAS office.
↵ ¶ GpX (gene product) refers to the monomeric product of gene X, whereas PX refers to the matured, multimeric complex of gpX's that has assembled into the structure that is found in the phage T4 virion.
↵ ‖ There is conflicting evidence as to whether the gene 34, 36, and 37 segments of the tail fibers are homodimers (8, 9) or homotrimers (10). For the purposes of this work either case is possible because the monomers are arranged in an overall parallel fashion (i.e., N termini together at one end of the mature protein and C termini at the other end). This means that insertions, deletions, or modifications in the protein monomers will be located at identical positions in the mature dimer/trimer. For simplicity, we will refer to the proteins as forming dimers.