About

Chris Fromme, Ph.D., is the Principal Investigator at the Weill Institute for Cell and Molecular Biology within the Department of Molecular Biology and Genetics at Cornell University. His laboratory is part of the Cornell CALS program and is located in Weill Hall in Ithaca, NY. The lab's focus is on cell and molecular biology, with research activities likely centered around understanding cellular processes at the molecular level, although specific research details are not provided on the page. Dr. Fromme's role involves leading research efforts, mentoring lab members including postdoctoral associates, graduate students, and undergraduates, and contributing to the scientific community through his work at Cornell University.

Research topics

• Chemistry
• Cell biology
• Biology
• Biochemistry

Selected publications

• Structural details of GEF‐mediated Sar1 activation

  The FASEB Journal · 2020

  Senior authorCorresponding
  • Cell biology
  • Chemistry
  • Biology

  The first trafficking step of the eukaryotic secretory pathway is the packaging of cargo proteins into COPII‐coated vesicles that exit the endoplasmic reticulum (ER). COPII vesicle coat proteins are recruited to the ER membrane via direct interaction with the activated (GTP‐bound) form of the Sar1 GTPase. Sar1 is activated on the surface of the ER by Sec12, a membrane‐anchored GEF (guanine nucleotide exchange factor). Here we report the crystal structure of the complex between Sar1 and the cytoplasmic domain of Sec12, representing a snapshot of the activation reaction. This structure provides detailed insight into the mechanism of Sar1 activation. The structure reveals that despite structural homology to the RCC1 GEF, a distinct surface of the beta‐propeller fold of Sec12 interacts with Sar1 to displace nucleotide. The structural results suggest that the cytoplasmic domain of Sec12 may adopt an unexpected orientation relative to the membrane surface. This orientation would position Sar1 on the ER membrane so that binding to GTP and engagement of its amphipathic N‐terminal helix with the lipid leaflet can occur simultaneously. Together with accompanying functional data, our results provide a structural explanation for the critical regulatory step of COPII vesicle biogenesis. Support or Funding Information This work was funded by the National Institutes of Health grant R01GM116942 to J.C.F. Alfred P. Sloan Foundation Fellowship and NSF GRFP DGE‐1650441 to A.J.

  PublisherDOI

• In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

  bioRxiv (Cold Spring Harbor Laboratory) · 2019-07-13 · 10 citations

  preprintOpen access

  Abstract Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here we present a comprehensive phosphoproteomic dataset for budding yeast, comprised of over 30,000 high confidence phosphorylation sites identified by mass spectrometry. This single dataset nearly doubles the size of the known phosphoproteome in budding yeast and defines a set of cell cycle-regulated phosphorylation events. With the goal of enhancing the identification of functional phosphorylation events, we performed computational positioning of phosphorylation sites on available 3D protein structures and systematically identified events predicted to regulate protein complex architecture. Results reveal a large number of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic “clashes” predicted to disrupt the interaction. Phosphorylation site mutants experimentally validate our predictions and support a role for phosphorylation in negatively regulating protein-protein interactions. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.

  PublisherOA PDFDOI

• Deciphering TRAPP complex function in yeast

  The FASEB Journal · 2018-04-01

  articleSenior author

  All eukaryotes contain organelles that perform specialized functions essential for life. The Golgi complex, an organelle that is important for transport of cellular material, serves as the “Grand Central Station” of the cell by receiving, then sorting proteins and membranes to various locations. Many steps of vesicular trafficking at the Golgi complex are regulated by several families of small GTPases, which modulate between an active and inactive state. One particularly interesting GTPase is Rab1, which also has an established role in autophagy. Rab1 is activated by a g uanine nucleotide e xchange f actor (GEF), a process that is conserved from mammals to yeast. Discordantly, mammals contain two protein complexes named TRAPPII and TRAPPIII ( tra nsport p rotein p article) which activate Rab1; while in yeast, four (TRAPPI ‐ TRAPPIV) have been implicated as GEFs in Ypt1 (Rab1 homolog) activation. Yeast TRAPP complexes share a core set of six subunits. Additional subunits are thought to regulate the complex by adding substrate and compartmental specificity. TRAPPII contains four more subunits, while TRAPPIII and TRAPPIV include one additional subunit. Importantly, the precise functions of the accessory subunits remain unclear. We demonstrate that TRAPPII and TRAPPIII are the only two complexes present in yeast cells, which is consistent with findings in mammalian cells, by quantifying isolated TRAPP complexes and simultaneously monitoring the localization of all TRAPP complexes in vivo. We also find that, using an in vitro fluorescent nucleotide exchange assay, TRAPPIII activates Ypt1 more effectively than the other complexes. Concurrently, we notice that Trs85 localizes to the Golgi complex and that Ypt1 is mislocalized in vivo in the absence of the TRAPPIII‐specific subunit, Trs85. Additionally, using an in vitro membrane binding assay, we find that Trs85 has an affinity for membranes. These findings suggest that there are only two TRAPP complexes in yeast, and that TRAPPIII is involved in trafficking at the Golgi complex in addition to its established role in autophagy. Taken together, our model suggests that the main role of Trs85 in the TRAPPIII complex is to bring the catalytic core close to a membrane surface, localizing the active site to the right compartment in an orientation that facilitates localization and activation of Ypt1. Support or Funding Information This material is based upon work supported by the NSF GRFP under Grant DGE‐1144153, by NIH/NIGMS Grant R01GM116942, and by the Alfred P. Sloan Foundation. Any opinions, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF, NIH, the Sloan Foundation or their trustees, officers, or staff. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

  PublisherDOI

• The HUS‐box is required for allosteric regulation of the Sec7 Arf‐GEF

  The FASEB Journal · 2018-04-01

  articleSenior author

  The Golgi complex is the central membrane and protein sorting station of eukaryotic cells. Activation of Arf GTPases is essential for vesicle formation via recruitment of cargo adaptors and coat proteins necessary for Golgi trafficking. Arf activation is spatially and temporally regulated by distinct guanine nucleotide exchange factors (GEFs) at different Golgi compartments. The yeast Arf‐GEF Sec7 is a conserved and essential activator of Arf1 at the trans‐Golgi network. Sec7 contains a highly conserved regulatory region, the HUS‐box, with an unknown mechanistic role. In this study we explore how the HUS‐box, which is N‐terminal to the catalytic domain, acts together with C‐terminal regulatory domains in the allosteric activation of Sec7. We show that mutation of the HUS‐box disturbs positive feedback and allosteric activation of Sec7 by the GTPase Ypt31, the yeast Rab11 homolog. Taken together, our data lead to a model in which the inter‐ and intramolecular interactions of the HUS‐box and C‐terminus are necessary for the allosteric activation of Sec7. Support or Funding Information This work was supported by NIH/NIGMS award R01GM09861 to J.C.F. and NIH/NIGMS training grant T32GM007273 to S.L.H. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

  PublisherDOI

• Faculty Opinions recommendation of Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2017-04-03

  dataset1st authorCorresponding
  PublisherDOI

• Semi Automated Ferrous Material Scouring System (SAFMSS)

  2016-03-14

  articleSenior author

  Abstract : The project was focused on developing a Semi-Autonomous System that could be utilized for the remediation of large scale range clearing projects. The major goals associated with the development of this system were to: increase the speed of range clearing operations; improve personnel safety by removing workers from dangerous areas; and, decrease cost to the government by decreasing personnel costs and days to completion.

  Publisher

• Faculty Opinions recommendation of A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2016-01-20

  datasetOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Faculty Opinions recommendation of A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2016-04-01

  dataset1st authorCorresponding
  PublisherDOI

• Faculty Opinions recommendation of TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2016-09-15

  dataset1st authorCorresponding
  PublisherDOI

• Faculty Opinions recommendation of Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2015-02-24

  dataset1st authorCorresponding
  PublisherDOI

Frequent coauthors

• Aaron M.N. Joiner

  University of California, Berkeley

  3 shared

• Ethan J. Sanford

  Cornell University

  1 shared

• Shagun Gupta

  Cornell University

  1 shared

• Michael C. Lanz

  Chan Zuckerberg Initiative (United States)

  1 shared

• Haiyuan Yu

  Cornell University

  1 shared

• Kumar Yugandhar

  Cornell University

  1 shared

• Stephanie Vega

  Cornell University

  1 shared

• Herman Herman

  Tadulako University

  1 shared

Labs

• The Fromme LabPI

Awards & honors

• 2021 Robert H. Foote Mid-Career Teaching Award
• 2018 Mentor of the Year, Southern Regional Education Board
• 2018 Faculty Champion Award
• 2016 Fellow, John Simon Guggenheim Memorial Foundation