Alternative splicing can produce multiple mRNA transcripts from a single gene sequence, thereby expanding the number of protein sequences encoded by the genome of a cell. Protein isoforms from alternative splicing may have different functions owing to their different sequences, but examples of alternative splicing producing isoforms with different structures are lacking. CD46 (membrane cofactor protein) is a cell surface glycoprotein that helps protect human cells from destruction by the complement system and a receptor for several human pathogens. It is alternatively spliced into two main isoforms in the extracellular region (BC and C) that differ by the presence or absence of 15 amino acids. Based on existing structural data, we hypothesized that the C isoforms of CD46 form oligomers while the BC isoforms exist as monomers on the cell surface. Proteins on the HeLa cervical cell surface were treated using a membrane‐impermeable crosslinker, then subjected to denaturing gel electrophoresis and western blotting. HeLa cells express both BC and C isoforms of CD46, but only the C isoform changed its electrophoretic mobility to a higher molecular weight after crosslinking. A549 lung epithelial cells express only the BC isoforms, and the molecular weights of their CD46 proteins were unaffected by the crosslinker. These results indicate that CD46 can exist as monomeric and oligomeric spliceoforms. We show that alternative splicing can produce proteins with different quaternary structures from the same gene. Support or Funding Information Funded by University of Richmond School of Arts & Sciences This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

10.1096/fasebj.2018.32.1_supplement.650.9

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CD46 Is a Protein Receptor for Human Adenovirus Type 64

Viruses (2024)

Eugene Wu Alexander Robertson Haiqing Zhu Corina Stasiak Laura A. Murray‐Nerger

Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination. Here, we demonstrate that, like HAdV-D37, HAdV-D64 virions bind directly to CD46 and that CD46 and sialic acid also function as receptors for HAdV-D64 on multiple cell types. Expression of CD46 on CD46-negative cells conferred susceptibility to HAdV-D64 entry. Specifically blocking HAdV-D64 binding to CD46 on the host cell surface strongly inhibits viral entry and gene delivery into multiple cell lines that represent target tissues. We show that CD46 is expressed on human conjunctival epithelial cells and directly binds to the HAdV-D64 virion. Our results suggest that HAdV-D64 may be used to deliver genes to target conjunctival cells and that interrupting HAdV-D64 entry through its interaction with CD46 may prevent or lessen adenovirus-associated ocular disease.

10.3390/v16121827

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