John B. McCullough

John B. McCullough, PhD, BSc

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

Research Statement

I am an experienced biochemist with over 20 years of productive research in the ESCRT field, with a particular focus on the structure and function of the membrane-remodeling ESCRT-III class of proteins. I published the first high resolution structure of an ESCRT-III protofilament in its assembled state and am co-first author on our upcoming publication that describes a novel ESCRT-III association with DNA bridges. My approaches include cryo-EM and biochemical analyses of the interactions between ESCRT-III family members. In addition to my research on ESCRT structure and function, I am the scientific manager of the NIAID-funded U54 CHEETAH Center for the Structural Biology of HIV Infection, Restriction and Viral Dynamics.

Education History

Undergraduate National University of Ireland, Galway
 BSc
Doctoral Training University of Liverpool
 PhD
Postdoctoral Training University of Utah
 Postdoctoral Training

Selected Publications

Journal Article

  1. Hammond DE, Carter S, McCullough J, Urbe S, Vande Woude G, Clague MJ (2003). Endosomal dynamics of Met determine signaling output. Mol Biol Cell, 14(4), 1346-54.
  2. Dobro MJ, Samson RY, Yu Z, McCullough J, Ding HJ, Chong PL, Bell SD, Jensen GJ (2013). Electron cryotomography of ESCRT assemblies and dividing Sulfolobus cells suggests that spiraling filaments are involved in membrane scission. Mol Biol Cell, 24(15), 2319-27.
  3. Urbe S, McCullough J, Row P, Prior IA, Welchman R, Clague MJ (2006). Control of growth factor receptor dynamics by reversible ubiquitination. Biochem Soc Trans, 34(Pt 5), 754-6.
  4. Row PE, Prior IA, McCullough J, Clague MJ, Urbe S (2006). The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J Biol Chem, 281(18), 12618-24.
  5. Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI, Hill CP (2020). Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. J Biol Chem, 295(2), 435-443.
  6. McCullough J, Clague MJ, Urbe S (2004). AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol, 166(4), 487-92.
  7. McCullough J, Fisher RD, Whitby FG, Sundquist WI, Hill CP (2008). ALIX-CHMP4 interactions in the human ESCRT pathway. Proc Natl Acad Sci U S A, 105(22), 7687-91.
  8. McCullough J, Clippinger AK, Talledge N, Skowyra ML, Saunders MG, Naismith TV, Colf LA, Afonine P, Arthur C, Sundquist WI, Hanson PI, Frost A (2015). Structure and membrane remodeling activity of ESCRT-III helical polymers. Science, 350(6267), 1548-51.
  9. McCullough J, Row PE, Lorenzo O, Doherty M, Beynon R, Clague MJ, Urbe S (2006). Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Curr Biol, 16(2), 160-5.
  10. Bajorek M, Schubert HL, McCullough J, Langelier C, Eckert DM, Stubblefield WM, Uter NT, Myszka DG, Hill CP, Sundquist WI (2009). Structural basis for ESCRT-III protein autoinhibition. Nat Struct Mol Biol, 16(7), 754-62.
  11. McCullough J, Sundquist WI (2014). Putting a finger in the ring. Nat Struct Mol Biol, 21(12), 1025-7.
  12. Nguyen HC, Talledge N, McCullough J, Sharma A, Moss FR 3rd, Iwasa JH, Vershinin MD, Sundquist WI, Frost A (2020). Membrane constriction and thinning by sequential ESCRT-III polymerization. Nat Struct Mol Biol, 27(4), 392-399.
  13. Morita E, Sandrin V, McCullough J, Katsuyama A, Baci Hamilton I, Sundquist WI (2011). ESCRT-III protein requirements for HIV-1 budding. Cell Host Microbe, 9(3), 235-42.
  14. Romanov V, McCullough J, Gale BK, Frost A (2019). A tunable microfluidic device enables cargo encapsulation by cell-or organelle-sized lipid vesicles comprising asymmetric lipid bilayers . Adv Biosyst, 2019(1900010), https://doi.org/10.1002/adbi.201900010.
  15. Talledge N, McCullough J, Wenzel D, Nguyen HC, Lalonde MS, Bajorek M, Skalicky J, Frost A, Sundquist WI (August 7, 2018). The ESCRT-III proteins IST1 and CHMP1B assemble around nucleic acids. BioRxiv.
  16. Lara Rheinemann, Diane Miller Downhour, Kate Bredbenner, Gaelle Mercenne, Kristen A Davenport, Phuong Tieu Schmitt, Christina R Necessary, John mcCullough, Anthony P Schmitt, Sanford M Simon, Wesley I Sundquist, Nels C Eld (2021). RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis. Cell, 184(21), 5419-5431.

Review

  1. McCullough J, Colf LA, Sundquist WI (2013). Membrane fission reactions of the mammalian ESCRT pathway. [Review]. Annu Rev Biochem, 82, 663-92.
  2. McCullough J, Frost A, Sundquist WI (2018). Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes. [Review]. Annu Rev Cell Dev Biol, 34, 85-109.

Book Chapter

  1. McCullough J, Clague MJ, Urbé S (2007). Ubiquitin and protein sorting to the lysosome. In Mayer RJ, Ciechanover A, Rechsteiner M (Eds.), Protein Degradation: Cell Biology of the Ubiquitin-Proteasome System (Volume 3, pp. 76-102). Weinheim: Wiley-VCH.

Commentary

  1. McCullough J, Sundquist WI (2020). Membrane Remodeling: ESCRT-III Filaments as Molecular Garrotes. Curr Biol, 30(23), R1425-R1428.
  2. McCullough J, Sundquist WI (2025). Thylakoid membrane remodeling by VIPP1 ESCRT-III-like filaments. Nature structural & molecular biology, 32(3), 414-417.