Architecture of the Herpes Simplex Virus Major Capsid Protein Derived from Structural Bioinformatics

• Published in: Journal of molecular biology 2003-08, Vol.331 (2), p.447-456
• Main Authors: Baker, Matthew L., Jiang, Wen, Bowman, Brian R., Hong Zhou, Z., Quiocho, Florante A., Rixon, Frazer J., Chiu, Wah
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Annexins - chemistry; Capsid Proteins - chemistry; Computational Biology; Cryoelectron Microscopy; Crystallography, X-Ray; Databases as Topic; electron cryomicroscopy; fold recognition; Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Folding; protein structure; Protein Structure, Secondary; Protein Structure, Tertiary; secondary structure; Sequence Homology, Amino Acid; Simplexvirus - chemistry; Software; virus
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/S0022-2836(03)00696-X

The dispositions of 39 α helices of greater than 2.5 turns and four β sheets in the major capsid protein (VP5, 149 kDa) of herpes simplex virus type 1 were identified by computational and visualization analysis from the 8.5 Å electron cryomicroscopy structure of the whole capsid. The assignment of helices in the VP5 upper domain was validated by comparison with the recently determined crystal structure of this region. Analysis of the spatial arrangement of helices in the middle domain of VP5 revealed that the organization of a tightly associated bundle of ten helices closely resembled that of a domain fold found in the annexin family of proteins. Structure-based sequence searches suggested that sequences in both the N and C-terminal portions of the VP5 sequence contribute to this domain. The long helices seen in the floor domain of VP5 form an interconnected network within and across capsomeres. The combined structural and sequence-based informatics has led to an architectural model of VP5. This model placed in the context of the capsid provides insights into the strategies used to achieve viral capsid stability.