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Christopher P. Hill

Distinguished Professor and Co-Chair of Biochemistry

Hill Photo

B.A. University of York, United Kingdom

D.Phil. University of York, United Kingdom



Chris Hill's Lab Page

Chris Hill's PubMed Literature Search


Molecular Biology Program

Biological Chemistry Program

Protein Structure & Function


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 and electron microscopy. Our interests include HIV, nucleosome remodeling and reorganization, and proteasome activation.

We are interested in many facets of the HIV-1 life cycle, including viral entry, viral budding, virion architecture, and virion maturation. We are also interested in the cellular innate immunity factors that have evolved to counteract retroviral replication. Our work on HIV is collaborative through the CHEETAH program (see lab web site for information). One example of our studies in this area is provided by ALIX. We have determined multiple crystal structures of this cellular protein in a variety of functional states. Complexes with fragments of viral Gag proteins have revealed how viral late domains recruit ALIX to help drive virus budding. Complexes with fragments of ESCRT-III proteins reveal, in turn, how ALIX recruits components of the MVB pathway that actually drive the membrane pinching process. In all cases, our structural studies are complemented by biochemical and functional studies that are performed in our lab or by collaborating laboratories.

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 determinations of 1.1 MDa proteasome- activatorcomplexes shows how proteasomes are activated. Currently, we are using mutagenesis, biochemistry, and structural methods to understand how this and other proteasome activators work.

Hill Top Figure

Top -- proteasome:activator complex.
Bottom -- Structure of ALIX in complex with ESCRT-III and HIV-1 partners.


  1. Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill CP. (2017) A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. Elife. 2017 Aug 16;6. pii: e28723. doi: 10.7554/eLife.28723.

  2. VanderLinden RT, Hemmis CW, Yao T, Robinson H, Hill CP. (2017) Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. J Biol Chem. 292(23):9493-9504.

  3. Monroe N, Han H, Shen PS, Sundquist WI, Hill CP. (2017) Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase. Elife. Apr 5;6. pii: e24487. doi: 10.7554/eLife.24487.

  4. Monroe N, Hill CP. (2016) Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines. J Mol Biol. 428:1897-911.
  5. Kemble DJ, McCullough LL, Whitby FG, Formosa T, Hill CP. (2015) FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs. Mol Cell. 60:294-306.
  6. Han H, Monroe N, Votteler J, Shakya B, Sundquist WI, Hill CP. (2015) Binding of Substrates to the Central Pore of the Vps4 ATPase Is Autoinhibited by the Microtubule Interacting and Trafficking (MIT) Domain and Activated by MIT Interacting Motifs (MIMs). J Biol Chem 290:13490-9.
  7. VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP. (2015) Structural basis for the activation and inhibition of the UCH37 deubiquitylase.  Molecular Cell 57:901-11.
  8. Monroe N, Han H, Gonciarz MD, Eckert DM, Karren MA, Whitby FG, Sundquist WI, Hill CP. (2014) The oligomeric state of the active Vps4 AAA ATPase. J Mol Biol 426:510-25.
  9. Hill CP, Sundquist WI. (2013) Building a super elongation complex for HIV. Elife 2:e00577.
  10. Kemble DJ, Whitby FG, Robinson H, McCullough LL, Formosa T, Hill CP. (2013) Structure of the Spt16 middle domain reveals functional features of the histone chaperone FACT. J Biol Chem. 288:10188-94.
  11. Kish-Trier E, Hill CP. (2013) Structural biology of the proteasome. Annu Rev Biophys 42:29-49.
  12. Schubert HL, Wittmeyer J, Kasten MM, Hinata K, Rawling DC, Héroux A, Cairns BR, Hill CP. (2013) Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler. Proc Natl Acad Sci U S A 110:3345-50.
  13. Stadtmueller BM, Kish-Trier E, Ferrell K, Petersen CN, Robinson H, Myszka DG, Eckert DM, Formosa T, Hill CP. (2012) Structure of a proteasome Pba1-Pba2 complex: implications for proteasome assembly, activation, and biological function. J Biol Chem 287:37371-82.
  14. Tian G, Park S, Lee MJ, Huck B, McAllister F, Hill CP, Gygi SP, Finley D. (2011) An asymmetric interface between the regulatory and core particles of the proteasome. Nat Struct Mol Biol 18:1259-67.
  15. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W. (2011) UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci 14:874-80.
  16. Stadtmueller BM, Hill CP. (2011) Proteasome activators. Molecular Cell 41:8-19.
  17. McDonald SM, Close D, Xin H, Formosa T, Hill CP. (2010) Structure and biological importance of the Spn1-Spt6 interaction, and its regulatory role in nucleosome binding. Molecular Cell 40:725-735.
  18. Schubert HL, Zhai Q, Sandrin V, Eckert DM, Garcia-Maya M, Saul L, Sundquist WI, Steiner RA, Hill CP. (2010) Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc Natl Acad Sci USA 107:17951-17956.
  19. Sadre-Bazzaz K, Whitby FG, Robinson H, Formosa T, Hill CP. (2010) Structure of a Blm10 complex reveals common mechanisms for proteasome binding and gate opening. Molecular Cell 37:728-35.
  20. Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M. (2009) X-ray structures of the hexameric building block of the HIV capsid. Cell 137:1282-92.
  21. Bajorek M, Schubert HL, McCullough J, Langelier C, Eckert DM, Stubblefield WB, Uter NT, Myszka DG, Hill CP, Sundquist WI. (2009) Structural Basis for ESCRT-III Protein Autoinhibition. Nat Struct Mol Biol 16:754-62.
  22. McCullough J, Fisher RD, Whitby FG, Sundquist WI, Hill CP. (2008) ALIX-CHMP4 interactions in the human ESCRT pathway. PNAS 105:7687-91.
  23. Zhai Q, Fisher RD, Chung HY, Myszka DG, Sundquist WI, Hill CP. (2008) Structural and functional studies of ALIX interactions with YPX(n)L late domains of HIV-1 and EIAV. Nat. Struct. Mol. Biol. 15:43-9.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.

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Last Updated: 9/8/17