Structure function studies of vaccinia virus host range protein K1 reveal a novel functional surface for ankyrin repeat proteins

Yongchao Li, Xiangzhi Meng, Yan Xiang, Junpeng Deng

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Poxvirus host tropism at the cellular level is regulated by virus-encoded host range proteins acting downstream of virus entry. The functioning mechanisms of most host range proteins are unclear, but many contain multiple ankyrin (ANK) repeats, a motif that is known for ligand interaction through a concave surface. We report here the crystal structure of one of the ANK repeat-containing host range proteins, the vaccinia virus K1 protein. The structure, at a resolution of 2.3 Å, showed that K1 consists entirely of ANK repeats, including seven complete ones and two incomplete ones, one each at the N and C terminus. Interestingly, Phe82 and Ser83, which were previously shown to be critical for K1's function, are solvent exposed and located on a convex surface, opposite the consensus ANK interaction surface. The importance of this convex surface was further supported by our additional mutagenesis studies. We found that K1's host range function was negatively affected by substitution of either Asn51 or Cys47 and completely abolished by substitution of both residues. Cys47 and Asn51 are also exposed on the convex surface, spatially adjacent to Phe82 and Ser83. Altogether, our data showed that K1 residues on a continuous convex ANK repeat surface are critical for the host range function, suggesting that K1 functions through ligand interaction and does so with a novel ANK interaction surface.

Original languageEnglish (US)
Pages (from-to)3331-3338
Number of pages8
JournalJournal of Virology
Volume84
Issue number7
DOIs
StatePublished - Apr 2010

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Ankyrin Repeat
ankyrins
Vaccinia virus
Host Specificity
host range
Ankyrins
Proteins
proteins
Viral Tropism
Ligands
Poxviridae
Virus Internalization
Mutagenesis
viruses
tropisms
crystal structure
mutagenesis
Viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Structure function studies of vaccinia virus host range protein K1 reveal a novel functional surface for ankyrin repeat proteins. / Li, Yongchao; Meng, Xiangzhi; Xiang, Yan; Deng, Junpeng.

In: Journal of Virology, Vol. 84, No. 7, 04.2010, p. 3331-3338.

Research output: Contribution to journalArticle

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