Abstract

Large biological structures are assembled from smaller, often symmetric, sub-structures. However, asymmetry among sub-structures is fundamentally important for biological function. An extreme form of asymmetry, a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, is found in numerous icosahedral viruses, including tailed bacteriophages, herpesviruses, and archaeal viruses. This vertex is critical for driving capsid assembly, DNA packaging, tail attachment, and genome ejection. Here, we report the near-atomic in situ structure of the symmetry-mismatched portal vertex from bacteriophage T4. Remarkably, the local structure of portal morphs to compensate for symmetry-mismatch, forming similar interactions in different capsid environments while maintaining strict symmetry in the rest of the structure. This creates a unique and unusually dynamic symmetry-mismatched vertex that is central to building an infectious virion.

Highlights

  • Large biological structures are assembled from smaller, often symmetric, sub-structures

  • The viral portal vertex consists of a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, making it the unique vertex of an icosahedral viral capsid[2,8]

  • It is an extreme form of symmetry mismatch where the sub-assemblies, the portal and the capsid, have completely different structures, symmetries, and functions

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Summary

Introduction

Large biological structures are assembled from smaller, often symmetric, sub-structures. An extreme form of asymmetry, a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, is found in numerous icosahedral viruses, including tailed bacteriophages, herpesviruses, and archaeal viruses. This vertex is critical for driving capsid assembly, DNA packaging, tail attachment, and genome ejection. The viral portal vertex consists of a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, making it the unique vertex of an icosahedral viral capsid[2,8] It is an extreme form of symmetry mismatch where the sub-assemblies, the portal and the capsid, have completely different structures, symmetries, and functions. The tailed bacteriophage T4 which infects Escherichia coli bacterium is one of the most well-characterized viruses, an exceptional model system in molecular biology, and a powerful platform for gene, vaccine, and therapeutic molecule delivery[18,19,20]

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