Protein-protein complexes and methods of using same
OwnerLoic Giot, Andrew Eisen +1inventors
InventorsLoic Giot, Andrew Eisen, David A. Lewin
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Abstract
The invention provides complexes of at least two polypeptides, and methods of using the same. Purified complexes of two polypeptides are provided, including chimeric complexes, and chimeric polypeptides and complexes thereof are also provided, as are nucleic acids encoding chimeric polypeptides and vectors and cells containing the same. Also provided are methods of identifying agents that disrupt polypeptide complexes, methods of identifying complex or polypeptide in a sample, and for removing the same, methods of determining altered expression of a polypeptide in a subject, and methods of treating/preventing disorders involving altered levels of complex or polypeptide.
Claims44
A purified complex comprising a first polypeptide and a second polypeptide, wherein
- said first polypeptide comprises an amino acid sequence of a polypeptide selected from the group consisting of the polypeptides recited in Table 1, column 2, and wherein said second polypeptide comprises an amino acid sequence of the corresponding polypeptide recited in Table 1, column 3;
- or
- said first and second polypeptide comprise the amino acid sequences of a first polypeptide-second polypeptide complex selected from the group consisting of NAPA1-IP2, NAPA1-SYN16, NAPA1-SNAP29, NAPA1-SYN4, NAPA1-LZIP, NAPA1-SNAP25A, PPP1CC-NOV1, PPP1CC-NOV2, PPP1CC-NOV3, PPP1CC-NOV4, PPP1CC-NOV5, PPP1CC-PPP1R5, PPP1CC-KIAA0305, PPP1CC-STAU, PPP1CC-53BP2, PPP1CC-PPP1R10, S100A1-NOV6, S100A1-NOV7, S100A1-NOV8, S100A1-fibrinogen, S100A1-RanBPM, S100A1-profilin II-SV, S100B-NOV9, S100B-NOV10, S100B-NOV11, S100B-fibrinogen, S100B-KIAA0629, S100B-ATP6N1, S100B-synphilin I, S100B-NQO2, S100B-FHOS, S100B-S100A9, and S100B-S100A6.
A purified complex comprising a first polypeptide and a second polypeptide, wherein said first polypeptide comprises a region of amino acids of a polypeptide selected from the group consisting of the polypeptides recited in Table 1, column 2 sufficient to allow said first polypeptide to bind said second polypeptide, and wherein said second polypeptide comprises a region of amino acids of the corresponding polypeptide recited in Table 1, column 3 sufficient to bind said first polypeptide.
A method for inhibiting interaction of a vesicle trafficking-associated protein, with a ligand, the method comprising:
- contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex is selected from the group consisting of NAPA1-IP2, NAPA1-SYN16, NAPA1-SNAP29, NAPA1-SYN4, NAPA1-LZIP, and NAPA1-SNAP25A,
- thereby inhibiting interaction of said protein with said ligand.
A method for inhibiting interaction of a phosphatase I protein with a ligand, the the method comprising:
- contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex is selected from the group consisting of PPP1CC-NOV1, PPP1CC-NOV2, PPP1CC-NOV3, PPP1CC-NOV4, PPP1CC-NOV5, PPP1CC-PPP1R5, PPP1CC-KIAA0305, PPP1CC-STAU, PPP1CC-53BP2, and PPP1CC-PPP1R10,
- thereby inhibiting interaction of said protein with said ligand.
A method for inhibiting interaction of a calcium binding protein with a ligand, said method comprising the step of:
- contacting a complex comprising said protein and said ligand with an agent that disrupts said complex, wherein said complex is selected from the group consisting of S100A1-NOV6, S100A1-NOV7, S100A1-NOV8, S100A1-fibrinogen, S100A1-RanBPM, S100A1-profilin 11-SV, S100B-NOV9, S100B-NOV10, S100B-NOV11, S100B-fibrinogen, S100B-KIAA0629, S100B-ATP6N1, S100B-synphilin I, S100B-NQO2, S100B-FHOS, S100B-S100A9, and S100B-S100A6,
- thereby inhibiting interaction of said protein with said ligand.
An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
- (a) a mature form of an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13;
- (b) a variant of a mature form of an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of the amino acid residues from the amino acid sequence of said mature form;
- (c) an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13;
- and
- (d) a variant of an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13 wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of amino acid residues from said amino acid sequence.
34 The polypeptide of claim 33, wherein said polypeptide comprises the amino acid sequence of a naturally-occurring allelic variant of an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13.
The polypeptide of claim 34, wherein said allelic variant comprises an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13.
An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of
- (a) a nucleotide sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13;
- (b) a nucleotide sequence differing by one or more nucleotides from a nucleotide sequence selected from the group consisting of SEQ ID NOS:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, and 13, provided that no more than 20% of the nucleotides differ from said nucleotide sequence;
- (c) a nucleic acid fragment of (a);
- and
- (d) a nucleic acid fragment of (b).
Dependencies are inferred from the claim text.