Structure-based engineering of papillomavirus major capsid l1: controlling particle assembly.
The outer shell of the papillomavirus particle is comprised of 72 pentamers of the major capsid L1 protein arranged on a T = 7 icosahedral lattice. The recombinant L1 can form T = 7 virus-like particles in vitro. The crystal structure of a T = 7 papilloma virion has not yet been determined; however, the crystal structure of a T = 1 particle containing 12 pentamers is known. The T = 1 structure reveals that helix-helix interactions, through three helices-h2, h3, and h4-near the C-terminus of L1, mediate the inter-pentameric bonding that is responsible for T = 1 assembly. Based on the T = 1 crystal structure, we have generated a set of internal deletions to test the role of the three C-terminal helices in T = 7 assembly. We have demonstrated that the h2, h3, and h4 near the C-terminal end of L1 are important for the L1 structure and particle assembly. In particular, we found that h2 and h3 are essential for L1 folding and pentamer formation, whereas h4 is indispensable for the assembly of not only T1, but also of the T7 virus-like particle.
Bishop
Brooke
B
Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA. Brooke.Bishop@uchsc.edu
Dasgupta
Jhimli
J
Chen
Xiaojiang S
XS
D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005818:Genetic Engineering / Q000379:methods*; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000235:genetics; D052161:Human papillomavirus 18 / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D017384:Sequence Deletion; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly
D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; C063317:L1 protein, Human papillomavirus type 16; C480565:L1 protein, Human papillomavirus type 18