A binding site in nuclear hormone receptors is described and its structural coordinates are provided. The invention provides machine-readable data storage media comprising structure coordinates of Site II and computer systems comprising the machine-readable data storage media. The invention provides methods used in the design and identification of ligands of Site II and of modulators of nuclear hormone receptors. The invention provides ligands of Site II, modulators of NHRs, pharmaceutical compositions comprising modulators of NHRs, methods of modulating NHRs, and methods of treating diseases by administering modulators of an NHR. Also provided are methods of designing mutants, mutant NHRs, Site II binding assays, and models of Site II.

The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

The present invention provides a carrier for the delivery of molecules with biological function into both cellular and nuclear compartments. The carrier disclosed is heat shock protein 70 ("Hsp70"), or a fragment of Hsp70 as described herein, as a vehicle for directed, noninvasive delivery of molecules, such as proteins, peptides, or DNA, that may modulate cellular activity. The present invention also encompasses the use of Hsp70, or a fragment thereof, to modulate cellular activity, preferably to modulate nuclear activity in a cell or cells.

Novel compositions of immunosuppressants, such as cyclosporin, and polypeptide inhibitors of cytoplasmic protein nuclear translocation are disclosed. The compositions have, in addition to at least one immunosuppressant, at least one polypeptide inhibitor of nuclear translocation that has a signal sequence and at least one, preferably two, nuclear localization sequences. The compositions are useful as immunosuppression, antiviral and antitumor agents, preferably to prevent rejection of transplanted organs or tissue.

Novel polypeptide inhibitors of cytoplasmic protein nuclear translocation are disclosed. The inhibitors are comprised of a signal sequence and at least two nuclear localization sequences. The polypeptides are useful as immunosuppression, antiviral and antitumor agents.