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US 2002/0173622 A1Published application
Tsg101-GAGp6 interaction and use thereof
AssigneeMyriad Genetics, Inc.
InventorsDaniel Albert Wettstein, Scott Morham, Kenton Zavitz
Life of this patent
Estimating the term…
Abstract
Isolated protein complexes are provided comprising Tsg101 and HIV GAGp6. The protein complexes are useful in screening assays for selecting compounds effective in modulating the Tsg101-HIV GAGp6 interaction within the protein complexes.
Claims60
An isolated protein complex having a first protein which is Tsg101 or a homologue or derivative or fragment thereof interacting with a second protein which is HIV GAG polypeptide or a homologue or derivative or fragment thereof.
An isolated protein complex having a first protein which is Tsg101 or a homologue or derivative or fragment thereof interacting with a second protein which is HIV GAGp6 polypeptide or a homologue or derivative or fragment thereof.
An isolated protein complex comprising:
- (a) a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second protein selected from the group consisting of
- (1) HIV GAG polypeptide,
- (2) a HIV GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of HIV GAG polypeptide and capable of interacting with Tsg101,
- (3) HIV GAGp6 protein,
- (4) a HIV GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101,
- (5) a HIV GAGp6 fragment capable of interacting with Tsg101, and
- (6) a fusion protein containing said HIV GAG polypeptide, said HIV GAG polypeptide homologue, said HIV GAGp6 protein, said HIV GAGp6 homologue or said HIV GAGp6 fragment.
10 more elements
An isolated protein complex comprising a first protein which is Tsg101 or a homologue or derivative or fragment thereof interacting with a second protein which is a retrovirus GAG polypeptide containing the P(T/S)AP late domain motif or a homologue or derivative or fragment of said retrovirus GAG polypeptide.
An isolated protein complex comprising:
- (a) a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second protein selected from the group consisting of
- (1) a retrovirus GAG polypeptide having the P(T/S)AP late domain motif,
- (2) a homologue of said retrovirus GAG polypeptide, said homologue having an amino acid sequence at least 90% identical to that of said retrovirus GAG polypeptide and capable of interacting with Tsg101,
- (3) a fragment of said retrovirus GAG polypeptide, said fragment being capable of interacting with Tsg101, and
- (4) a fusion protein containing said retrovirus GAG polypeptide, said retrovirus GAG polypeptide homologue or said retrovirus GAG polypeptide fragment.
8 more elements
An isolated protein complex comprising:
- (a) a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second protein selected from the group consisting of
- (1) a primate lentivirus GAG polypeptide,
- (2) a primate lentivirus GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of said primate lentivirus GAG polypeptide and capable of interacting with Tsg101,
- (3) a primate lentivirus GAGp6 protein,
- (4) a primate lentivirus GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101,
- (5) a primate lentivirus GAGp6 fragment capable of interacting with Tsg101, and
- (6) a fusion protein containing said primate lentivirus GAG polypeptide, said primate lentivirus GAG polypeptide homologue, said primate lentivirus GAGp6 protein, said primate lentivirus GAGp6 homologue or said primate lentivirus GAGp6 fragment.
10 more elements
An isolated protein complex comprising:
- a first fusion protein having a Tsg101 protein fragment interacting with
- a second fusion protein containing a fragment of HIV GAG polypeptide.
A fusion protein having a first polypeptide covalently linked to a second polypeptide, wherein said first polypeptide is Tsg101 or a homologue or fragment thereof, and wherein said second polypeptide is HIV GAGp6 or a homologue or fragment thereof.
A method for selecting modulators of an interaction between a first protein and a second protein,
- (a) said first protein being selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) said second protein being selected from the group consisting of
- (1) HIV GAG polypeptide,
- (2) a HIV GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of HIV GAG polypeptide and capable of interacting with Tsg101,
- (3) HIV GAGp6 protein,
- (4) a HIV GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101,
- (5) a HIV GAGp6 fragment capable of interacting with Tsg101, and
- (6) a fusion protein containing said HIV GAG polypeptide, said HIV GAG polypeptide homologue, said HIV GAGp6 protein, said HIV GAGp6 homologue or said HIV GAGp6 fragment, said method comprising:
- contacting said first protein with said second protein in the presence of one or more test compounds;
- and
- determining the interaction between said first protein and said second protein.
13 more elements
A method for selecting modulators of an interaction between a first protein and a second protein,
- (a) said first protein being selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) said second protein being selected from the group consisting of
- (1) a retrovirus GAG polypeptide having the P(T/S)AP late domain motif,
- (2) a homologue of said retrovirus GAG polypeptide, said homologue having an amino acid sequence at least 90% identical to that of said retrovirus GAG polypeptide and capable of interacting with Tsg101,
- (3) a fragment of said retrovirus GAG polypeptide, said fragment being capable of interacting with Tsg101, and
- (4) a fusion protein containing said retrovirus GAG polypeptide, said retrovirus GAG polypeptide homologue or said retrovirus GAG polypeptide fragment, said method comprising:
- contacting said first protein with said second protein in the presence of one or more test compounds;
- and
- determining the interaction between said first protein and said second protein.
11 more elements
A method for selecting modulators of an interaction between a first polypeptide and a second polypeptide,
- (a) said first polypeptide being selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6, and
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain;
- and
- (b) said second polypeptide being selected from the group consisting of
- (1) HIV GAG polypeptide,
- (2) a HIV GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of HIV GAG polypeptide and capable of interacting with Tsg101,
- (3) HIV GAGp6 protein,
- (4) a HIV GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101, and
- (5) a HIV GAGp6 fragment capable of interacting with Tsg101, said method comprising:
- providing in a host cell a first fusion protein having said first polypeptide, and a second fusion protein having said second polypeptide, wherein a DNA binding domain is fused to one of said first and second polypeptides while a transcription-activating domain is fused to the other of said first and second polypeptides;
- providing in said host cell a reporter gene, wherein the transcription of the reporter gene is determined by the interaction between the first polypeptide and the second polypeptide;
- allowing said first and second fusion proteins to interact with each other within said host cell in the presence of a test compound;
- and
- determining the presence or absence of expression of said reporter gene.
13 more elements
A composition comprising:
- (a) a first expression vector having a nucleic acid encoding a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second expression vector having a nucleic acid encoding a second protein selected from the group consisting of
- (1) HIV GAG polypeptide,
- (2) a HIV GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of HIV GAG polypeptide and capable of interacting with Tsg101,
- (3) HIV GAGp6 protein,
- (4) a HIV GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101,
- (5) a HIV GAGp6 fragment capable of interacting with Tsg101, and
- (6) a fusion protein containing said HIV GAG polypeptide, said HIV GAG polypeptide homologue, said HIV GAGp6 protein, said HIV GAGp6 homologue or said HIV GAGp6 fragment.
10 more elements
A host cell comprising:
- (a) a first expression vector having a nucleic acid encoding a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second expression vector having a nucleic acid encoding a second protein selected from the group consisting of
- (1) HIV GAG polypeptide,
- (2) a HIV GAG polypeptide homologue having an amino acid sequence at least 90% identical to that of HIV GAG polypeptide and capable of interacting with Tsg101,
- (3) HIV GAGp6 protein,
- (4) a HIV GAGp6 homologue having an amino acid sequence at least 90% identical to that of HIV GAGp6 polypeptide and capable of interacting with Tsg101,
- (5) a HIV GAGp6 fragment capable of interacting with Tsg101, and
- (6) a fusion protein containing said HIV GAG polypeptide, said HIV GAG polypeptide homologue, said HIV GAGp6 protein, said HIV GAGp6 homologue or said HIV GAGp6 fragment.
10 more elements
A host cell comprising:
- (a) a first expression vector having a nucleic acid encoding a first protein which is selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- (b) a second expression vector having a nucleic acid encoding a second protein selected from the group consisting of
- (1) a retrovirus GAG polypeptide having the P(T/S)AP late domain motif,
- (2) a homologue of said retrovirus GAG polypeptide, said homologue having an amino acid sequence at least 90% identical to that of said retrovirus GAG polypeptide and capable of interacting with Tsg101,
- (3) a fragment of said retrovirus GAG polypeptide, said fragment being capable of interacting with Tsg101, and
- (4) a fusion protein containing said retrovirus GAG polypeptide, said retrovirus GAG polypeptide homologue or said retrovirus GAG polypeptide fragment.
8 more elements
A method for selecting a compound capable of inhibiting a protein-protein interaction between Tsg101 and HIV GAGp6, comprising:
- contacting a test compound with a protein selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said Tsg101 protein fragment;
- and
- determining whether said test compound is capable of binding said protein.
4 more elements
A method for selecting a compound capable of inhibiting a protein-protein interaction between Tsg101 and HIV GAGp6, comprising:
- providing atomic coordinates defining a three-dimensional structure of a protein selected from group consisting of
- (i) Tsg101 protein,
- (ii) a Tsg101 protein homologue having an amino acid sequence at least 90% identical to that of Tsg101 and capable of interacting with HIV GAGp6,
- (iii) a Tsg101 protein fragment containing the Tsg101 UEV domain, and
- (iv) a fusion protein containing said Tsg101 protein, said Tsg101 protein homologue or said TsglO1 protein fragment;
- and
- designing or selecting compounds capable of interacting with said protein based on said atomic coordinates.
4 more elements
An isolated antibody selectively immunoreactive with a protein complex comprising Tsg101 and HIV GAGp6.
Dependencies are inferred from the claim text.