Structural and functional characterization of human SGT and its interaction with Vpu of the human immunodeficiency virus type 1

Biochemistry. 2008 Sep 23;47(38):10123-31. doi: 10.1021/bi800758a. Epub 2008 Aug 30.

Abstract

The small glutamine-rich tetratricopeptide repeat protein (SGT) belongs to a family of cochaperones that interacts with both Hsp70 and Hsp90 via the so-called TPR domain. Here, we present the crystal structure of the TPR domain of human SGT (SGT-TPR), which shows that it contains typical features found in the structures of other TPR domains. Previous studies show that full-length SGT can bind to both Vpu and Gag of human immunodeficiency virus type 1 (HIV-1) and the overexpression of SGT in cells reduces the efficiency of HIV-1 particle release. We show that SGT-TPR can bind Vpu and reduce the amount of HIV-1 p24, which is the viral capsid, secreted from cells transfected with the HIV-1 proviral construct, albeit at a lower efficiency than full-length SGT. This indicates that the TPR domain of SGT is sufficient for the inhibition of HIV-1 particle release but the N- and/or C-terminus also have some contributions. The SGT binding site in Vpu was also identified by using peptide array and confirmed by GST pull-down assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Crystallography, X-Ray
  • HIV-1 / chemistry
  • HIV-1 / metabolism
  • HIV-1 / physiology*
  • Human Immunodeficiency Virus Proteins / chemistry
  • Human Immunodeficiency Virus Proteins / metabolism
  • Human Immunodeficiency Virus Proteins / physiology*
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Viral Regulatory and Accessory Proteins / chemistry*
  • Viral Regulatory and Accessory Proteins / metabolism
  • Viral Regulatory and Accessory Proteins / physiology

Substances

  • Anti-HIV Agents
  • Carrier Proteins
  • Human Immunodeficiency Virus Proteins
  • SGTA protein, human
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1

Associated data

  • PDB/2VYI