Amy E. Keating

Amy E. Keating

Professor of Biology and Biological Engineering

Amy E. Keating determines how proteins make specific interactions with one another and designs new, synthetic protein-protein interactions.

617-452-3398

Phone

68-622A

Office

Tau Zaman

Assistant

617-452-2717

Assistant Phone

Education

  • PhD, 1998, University of California, Los Angeles
  • SB, 1992, Physics, Harvard University

Research Summary

Our goal is to understand, at a high level of detail, how the interaction properties of proteins are encoded in their sequences and structures. We investigate protein-protein interactions by integrating data from high throughput assays, structural modeling, and bioinformatics with biochemical and biophysical experiments. Much of our work focuses on α-helical coiled-coil proteins, Bcl-2 apoptosis-regulating proteins, and protein domains that bind to short linear motifs.

Key Publications

  1. Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. Jenson, JM, Ryan, JA, Grant, RA, Letai, A, Keating, AE. 2017. Elife 6, .
    doi: 10.7554/eLife.25541PMID:28594323
  2. Data-driven prediction and design of bZIP coiled-coil interactions. Potapov, V, Kaplan, JB, Keating, AE. 2015. PLoS Comput. Biol. 11, e1004046.
    doi: 10.1371/journal.pcbi.1004046PMID:25695764
  3. SORTCERY-A High-Throughput Method to Affinity Rank Peptide Ligands. Reich, LL, Dutta, S, Keating, AE. 2015. J. Mol. Biol. 427, 2135-50.
    doi: 10.1016/j.jmb.2014.09.025PMID:25311858
  4. Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells. Foight, GW, Ryan, JA, Gullá, SV, Letai, A, Keating, AE. 2014. ACS Chem. Biol. 9, 1962-8.
    doi: 10.1021/cb500340wPMID:25052212
  5. Networks of bZIP protein-protein interactions diversified over a billion years of evolution. Reinke, AW, Baek, J, Ashenberg, O, Keating, AE. 2013. Science 340, 730-4.
    doi: 10.1126/science.1233465PMID:23661758

Recent Publications

  1. Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1. Frappier, V, Jenson, JM, Zhou, J, Grigoryan, G, Keating, AE. 2019. Structure 27, 606-617.e5.
    doi: 10.1016/j.str.2019.01.008PMID:30773399
  2. Peptide design by optimization on a data-parameterized protein interaction landscape. Jenson, JM, Xue, V, Stretz, L, Mandal, T, Reich, LL, Keating, AE. 2018. Proc. Natl. Acad. Sci. U.S.A. 115, E10342-E10351.
    doi: 10.1073/pnas.1812939115PMID:30322927
  3. PixelDB: Protein-peptide complexes annotated with structural conservation of the peptide binding mode. Frappier, V, Duran, M, Keating, AE. 2018. Protein Sci. 27, 1535-1537.
    doi: 10.1002/pro.3431PMID:30251349
  4. Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells. Rezaei Araghi, R, Bird, GH, Ryan, JA, Jenson, JM, Godes, M, Pritz, JR, Grant, RA, Letai, A, Walensky, LD, Keating, AE. 2018. Proc. Natl. Acad. Sci. U.S.A. 115, E886-E895.
    doi: 10.1073/pnas.1712952115PMID:29339518
  5. PixelDB: Protein-peptide complexes annotated with structural conservation of the peptide binding mode. Frappier, V, Duran, M, Keating, AE. 2018. Protein Sci. 27, 276-285.
    doi: 10.1002/pro.3320PMID:29024246
  6. Modular assembly of a protein nanotriangle using orthogonally interacting coiled coils. Park, WM, Bedewy, M, Berggren, KK, Keating, AE. 2017. Sci Rep 7, 10577.
    doi: 10.1038/s41598-017-10918-6PMID:28874805
  7. Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. Jenson, JM, Ryan, JA, Grant, RA, Letai, A, Keating, AE. 2017. Elife 6, .
    doi: 10.7554/eLife.25541PMID:28594323
  8. Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design. Foight, GW, Chen, TS, Richman, D, Keating, AE. 2017. Methods Mol. Biol. 1561, 213-232.
    doi: 10.1007/978-1-4939-6798-8_13PMID:28236241
  9. Combinatorial bZIP dimers display complex DNA-binding specificity landscapes. Rodríguez-Martínez, JA, Reinke, AW, Bhimsaria, D, Keating, AE, Ansari, AZ. 2017. Elife 6, .
    doi: 10.7554/eLife.19272PMID:28186491
  10. Generating High-Accuracy Peptide-Binding Data in High Throughput with Yeast Surface Display and SORTCERY. Reich, LL, Dutta, S, Keating, AE. 2016. Methods Mol. Biol. 1414, 233-47.
    doi: 10.1007/978-1-4939-3569-7_14PMID:27094295
More Publications

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