title: Structures and organization of adenovirus cement proteins provide insights into the role of capsid maturation in virus entry and infection.
abstract: Adenovirus cement proteins play crucial roles in virion assembly, disassembly, cell entry, and infection. Based on a refined crystal structure of the adenovirus virion at 3.8-Å resolution, we have determined the structures of all of the cement proteins (IIIa, VI, VIII, and IX) and their organization in two distinct layers. We have significantly revised the recent cryoelectron microscopy models for proteins IIIa and IX and show that both are located on the capsid exterior. Together, the cement proteins exclusively stabilize the hexon shell, thus rendering penton vertices the weakest links of the adenovirus capsid. We describe, for the first time to our knowledge, the structure of protein VI, a key membrane-lytic molecule, and unveil its associations with VIII and core protein V, which together glue peripentonal hexons beneath the vertex region and connect them to the rest of the capsid on the interior. Following virion maturation, the cleaved N-terminal propeptide of VI is observed, reaching deep into the peripentonal hexon cavity, detached from the membrane-lytic domain, so that the latter can be released. Our results thus provide the molecular basis for the requirement of maturation cleavage of protein VI. This process is essential for untethering and release of the membrane-lytic region, which is known to mediate endosome rupture and delivery of partially disassembled virions into the host cell cytoplasm.
authors: Departments of Integrative Structural and Computational Biology and reddyv@scripps.edu.
authors: Vijay S
authors: VS
authors: Reddy
authors: Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors: Glen R
authors: GR
authors: Nemerow
mesh_terms: D000260:Adenoviruses, Human / Q000737:chemistry* / Q000472:pathogenicity / Q000502:physiology; D055592:Biophysical Phenomena; D002213:Capsid / Q000737:chemistry / Q000502:physiology; D036022:Capsid Proteins / Q000737:chemistry / Q000502:physiology; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000502:physiology; D020836:Protein Structure, Quaternary; D055672:Static Electricity; D014758:Viral Core Proteins / Q000737:chemistry / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry* / Q000502:physiology; D019065:Virus Assembly / Q000502:physiology; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D014758:Viral Core Proteins; D014764:Viral Proteins; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus; C090876:polypeptide VI, adenovirus; C061289:virion protein mu, adenovirus
keywords: cement protein scaffold; human adenovirus; structure–function relationships