[No authors listed]
Changes in protein-protein interactions that occur in response to environmental cues are difficult to uncover and have been poorly characterized to date. Here we describe a yeast-based assay that allows many binary protein interactions to be assessed in parallel and under various conditions. This method combines molecular bar-coding and tag array technology with the murine dihydrofolate reductase-based protein-fragment complementation assay. A total of 238 protein-fragment complementation assay strains, each representing a unique binary protein complex, were tagged with molecular barcodes, pooled, and then interrogated against a panel of 80 diverse small molecules. Our method successfully identified specific disruption of the Hom3:Fpr1 interaction by the immunosuppressant FK506, illustrating the assay's capacity to identify chemical inhibitors of protein-protein interactions. Among the additional findings was specific cellular depletion of the Dst1:Rbp9 complex by the anthracycline drug doxorubicin, but not by the related drug idarubicin. The assay also revealed chemical-induced accumulation of several binary multidrug transporter complexes that largely paralleled increases in transcript levels. Further assessment of two such interactions (Tpo1:Pdr5 and Snq2:Pdr5) in the presence of 1,246 unique chemical compounds revealed a positive correlation between drug lipophilicity and the drug response in yeast.
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YBL039W-B, KAR4, CIT2, RVS161, RIM1, SYP1, YCR043C, ERS1, CDC39, OCA4, RGD2, GAT1, SEC4, FAR7, LSB3, SAP155, RIX7, GPI13, TPO1, HIF1, SPA2, FPS1, DNM1, SSK1, SNF7, STU2, RAX2, CCW12, HOG1, APS1, DPH5, PEX13, PWP1, YKE2, RCK2, GSY2, YPT6, YLR326W, NMA1, CHS5, MID2, VRP1, KAP95, ORM2, VPS38, ARC18, ROM2, SEC61, IKI3, AFG2, INA1, URA4, IMD3, FLC2, NUP60, FMP45, SHR3, LYS20, PHO13, YPD1, CDC36, DHH1, RDI1, LYS21, SNA4, ATG20, GET3, ASM4, ARP2, SNQ2, PST2, DOS2, UBC13, TVP15, SAC6, NUM1, CCT6, AKR1, PEX10, DPP1, PRO1, SWA2, ASP1, GPI8, YPQ2, RGA2, RVS167, GIN4, SLF1, PRS4, PIN4, FUI1, RIB1, YBL029C-A, LSM2, PEP1, GPI18, UGA2, CHS3, CSG2, SLM4, SEC18, SHE3, CNS1, FTH1, SDS24, YBP1, PCS60, GPX2, ENP1, RIB5, REI1, CHC1, KEX1, MPT5, PEX14, SEC27, LSG1, NUP145, MMS2, GUP1, HNM1, RPB9, TIF4632, DST1, CGR1, GET1, CKB1, SCL1, PMC1, ERP6, UFD1, YGR054W, ERG25, PAC10, SLX9, VOA1, YGR130C, PEX4, NSR1, GTR2, HGH1, HIP1, ELP2, SMI1, KEL2, APL6, SLH1, CAB4, YOR1, ERV29, SOP4, ATG27, TPK1, VPS35, INO1, SNA3, RPA34, YJL068C, PEP8, SNX4, BBC1, CYR1, MET3, SPC1, NUP85, CBF1, RFC2, STE24, CNB1, PRS1, MCD4, RCN1, RPT1, DHR2, DEF1, VPS24, ARC19, AUR1, DID4, MEH1, YKR023W, SIS2, PEX11, BRX1, PRS5, CKB2, CUE5, CKA2, VPS5, YVC1, VPS21, PIN2, TFC7, RPT5, PNO1, RPB2, PDR5, SEY1, LAS17, DED1, NOC2, WTM2, RPT4, VPH1, TPO4, MYO2, PRE10, MRS6, SSL2, TPM2, QDR2, NUP159, SLM1, MAM33, ARC15, NEO1, SYG1, NOT3, CKA1, CAP2, EMC5, FAA3, INP51, GTT1, GIM5, ALO1, TCB3, GTR1, ERV41, HUG1, IMD4, GAL80, AMD1, NDC1, PSP2, PPZ1, UBX2, ERV25, YAP1, YPT7, MVP1, YMR010W, PEX12, NUP116, PGM2, ADE17, RIM11, SIP5, RIM13, YMR221C, RRP5, GAD1, TPS3, TMA23, GOT1, ADE4, ELP6, MCK1, RFC3, CAF40, WSC2, GIS2, RPA49, YNL247W, SLA2, KEX2, URE2, PEX17, UBP10, GIM3, SRV2, FPR1, DCP2, DBP2, NST1, HHT2, VPS27, SSK2, RBD2, KEL3, FLC1, UIP4, KES1, HHO1, DBP1, HOS3, ELP4, YDC1, PDR12, LSP1, TIF6, APL4, VMA13, FCY1, NOT5, MRL1, PIS1, SCD6, SPN1, MEP3, TPO3, OCA5, HSE1, OSH7, YSC84, RPN1, MSC7, CIC1, QNS1, SAM35, GRE3, ERP5, KEL1, NMD3, CTR2, GPI16, WBP1, NOP16, GPA2, PRO3, GLN3, HOM3, FCY2, TRP2, LSM4, TMN3, SHO1, NSA2, FTR1, COG3
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