Protein science, biophysics and crystallography towards structure-based drug design.

Autophagy is a lysosomal degradation pathway that plays key roles in cellular homeostasis. We solved structures of autophagy-specific E1-E2 protein complexes and worked to understand the contributions of the autophagy-specific ubiquitin-like proteins to the specificity of their transfer to their E2 enzymes.Kaiser SE, Mao K, Taherbhoy AM, Yu S, Olszewski JL, Duda DM, Kurinov I, Deng A, Fenn TD, Klionsky DJ, Schulman BA. (2012) Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7–Atg3 and Atg7–Atg10 structures. Nat Struct Mol Biol. 19(12):1242-9. PMID: 23142976.

Quantifying cellular ubiquitin pools has long been an elusive goal because of the diversity of free and conjugated forms found in cells. We developed a quantitative mass spectrometry method to enable measurement of ubiquitin pools in biological samples.Kaiser SE, Riley BE, Shaler TA, Trevino RS, Becker CH, Schulman H, Kopito RR. (2011) Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools. Nat Methods. 8(8):691-6. PMID: 21743460.

My thesis work established that the VAP family of tail-anchored membrane proteins recruits cytosolic proteins containing an FFAT motif to the ER periphery by a mechanism that is conserved across eukaryotes. Kaiser SE, Brickner JH, Reilein AR, Fenn TD, Walter P, Brunger AT. (2005) Structural basis of FFAT Motif-mediated ER targeting. Structure. 13(7):1035-45. PMID: 16004875.