Christopher P. Hill
professor of biochemistry
B.A. University of York, United Kingdom
D.Phil. University of York, United Kingdom
Research
We study how macromolecular complexes assemble, move, and function to perform important biological processes. We use a range of molecular biological and biochemical techniques, with a major focus on determining 3-D structures by x-ray crystallography. Our interests include HIV assembly and budding, nucleosome reorganization and remodelling, and proteasome activation. Visit our lab website for details (https://wasatch.biochem.utah.edu/chris).
HIV assembly and maturation is driven by 5,000 copies of the Gag polyprotein. In collaboration with Wes Sundquist, we have determined structures of the Gag-derived matrix and capsid proteins, and developed models for how the assembling virus particle binds to membranes and undergoes a dramatic morphological change to produce an infectious virion. Currently, we are working on cellular proteins that function in the viral budding.
The proteasome is a multi-subunit complex that performs most of the proteolysis in the cytosol and nucleus of eukaryotic cells -- an activity that is essential for many fundamental processes. Our structure determinationof a 1.1 MDa proteasomeactivatorcomplex shows how proteasomes are activated and suggests how antigenic peptides are produced. Currently, we are using mutagenesis, biochemistry, and structural methods to understand how this and other proteasome activators work.
Top -- proteasome:activator complex.
Bottom -- Structure of ALIX in complex with ESCRT-III and HIV-1 partners.
References
1. Fisher RD, Chung H-Y, Zhai Q, Robinson H, Sundquist WI Hill CP (2007) Structural and Biochemical Studies of ALIX/AIP1 and Its Role in Retrovirus Budding. Cell 128:841-52
2. Alam SL, Langelier C, Whitby FG, Koirala S, Robinson H, Hill CP, Sundquist WI (2006) Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain. Nature Structural Molecular Biology 13:1029-30
3. VanDemark AP, Blanksma M, Ferris E, Heurox A, Hill CP, Formosa T (2006) The Structure of the yFACT Pob3-M Domain, Its Interaction with the DNA Replication Factor RPA, and a Potential Role in Nucleosome Deposition. Molecular Cell 22:363–374
4. Macbeth MR, Schubert HL, VanDemark AP, Ligam AT, Hill CP,Bass BL (2005) Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309(5740):1534-1539
5. Forster A, Masters EI, Whitby FG, Robinson H, Hill CP (2005) Implications for proteasome - PAN/PA 700 interactions from the 1-9A structure of a proteasome -11S activator complex. Molecular Cell 18:589-99
6. Sundquist WI, Schubert HL, Kelley BN, Hill GC, Holton JM, Hill CP (2004) Ubiquitin Recognition by the Human TSG101 Protein. Molecular Cell 13:783-9
7. Fisher RD, Wang B, Alam SL, Higginson DS, Robinson H, Sundquist WI, Hill, CP (2003) Structure and Ubiquitin Binding of the Ubiquitin Interacting Motif. J. Biol. Chem. 278:28976-84
8. Phillips JD, Whitby FG, Kushner JP, Hill CP (2003) Structural Basis for Tetrapyrole Coordination by Uroporphyrinogen Decarboxylase. EMBO J. 22:6225-33
9. Forster A, Whitby FG, Hill CP (2003) The Pore of Activated 20Sproteasomes has an Ordered 7-fold Symmetric Conformation. EMBO J. 22:4356-64
10. VanDemark AP, Hill CP (2003) Two-stepping with E1. Nature Structural Biology 10:244-246
11. Howard BR, Vajdos FF, Li S, Sundquist WI, Hill CP (2003) Structural insights into the catalytic mechanism of cyclophilin A. Nature Structural Biology 10:475-581
12. Brown PN, Hill CP, Blair DF (2002) Crystal structure of the middle and C-terminal domains of the flagellar rotor protein FliG. EMBO J. 21:3225-34
13. VanDemark AP, Hill CP (2002) Structural Basis of Ubiquitylation Current Opinion in Structural Biology 12:822-30
14. Whitby FG, Masters EI, Kramer L, Knowlton JR, Yao Y, Wang CC, Hill CP (2000) Structural basis for the activation of 20S proteasomes by 11S regulators. Nature 408:115-20
15. Li S, Hill CP, Sundquist WI, Finch JT (2000) Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409-13
16. Lloyd SA, Whitby FG, Blair DF, Hill CP (1999) Structure of the C-terminal domain of FliG, a component of the rotor in the bacterial flagellar motor. Nature 400:472-76
17. Knowlton JR, Johnston SC, Whitby FG, Realini CR, Rechsteiner MC Hill CP (1997) Structure of the proteasome regulator REGa(PA28a). Nature 390:639-43
18. Gamble TR, Yoo S, Vajdos FF, von Schwedler UK, Worthylake DK, Wang H, McCutcheon J, Sundquist WI, Hill CP (1997) Crystal structure of the C-terminal domain of HIV-1 capsid. Science 278:849-53
19. Gamble TR, Vajdos FF, Yoo S, Worthylake DK, Houseweart M, Sundquist WI, Hill CP (1996) Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87:1285-94
