The Faculty


Mechanisms of membrane protein biogenesis and quality control


B.S., Biology & Chemistry, Bates College, 1990

Ph.D., Biochemistry & Biophysics, UCSF, 1998

Research Summary

Our research interfaces biology and chemistry to understand the molecular mechanisms that underlie fundamental biological processes. Current research topics include:

1. Membrane protein biogenesis. How are newly synthesized membrane proteins targeted to the correct intracellular membrane? Once there, how are they inserted into the bilayer? A major focus in the lab is the study of co- and post-translational targeting and insertion pathways. Our long-term goal is to decipher common structural and mechanistic themes in membrane protein biogenesis.

2. Membrane protein quality control. What happens to membrane proteins that fail to engage the targeting and insertion machinery? What happens if they are inserted into the wrong membrane? Or when a properly inserted membrane protein becomes damaged? To help protect against damage caused by such events, cells have evolved complex pathways that identify and destroy misfolded and/or mislocalized membrane proteins.

Selected Publications

An ER translocon for multi-pass membrane protein biogenesis
McGilvray PT, Anghel SA, Sundaram A, Zhong F, Trnka MJ, Fuller JR, Hu H, Burlingame AL, Keenan RJ. (2020)
Elife, Aug 21;9:e56889. doi: 10.7554/eLife.56889.

The architecture of EMC reveals a path for membrane protein insertion
O'Donnell JP, Phillips BP, Yagita Y, Juszkiewicz S, Wagner A, Malinverni D, Keenan RJ, Miller EA, Hegde RS. (2020)
Elife, May 27;9:e57887. doi: 10.7554/eLife.57887.

A structural perspective on tail-anchored protein biogenesis by the GET pathway
Mateja, A and Keenan, RJ (2018) Current Opinion in Structural Biology, 51:195-202.
(doi: 10.1016/

Tail-anchored protein insertion by a single Get1/2 heterodimer
Zalisko, B.E., Chan, C., Denic, V., Rock, R.S. and Keenan, R.J. (2017) Cell Reports, 20:2287-2293.
(doi: 10.1016/j.celrep.2017.08.035)

Msp1 is a membrane protein dislocase for tail-anchored proteins
Wohlever ML, Mateja A, McGilvray PT, Day KJ and Keenan, RJ (2017) Molecular Cell, 67:194-202.
(doi: 10.1016/j.molcel.2017.06.019)

The GET system inserts the tail-anchored SYP72 protein into endoplasmic reticulum membranes
Srivistava R, Zalisko BE, Keenan RJ, Howell SH. (2017) Plant Physiol., 173:1137-1145.
(doi: 10.1104/pp.16.00928)

Ubiquilins chaperone and triage mitochondrial membrane proteins for degradation
Itakura, E., Zavodszky, E., Shao, S., Wohlever, M.L., Keenan, R.J., Hegde, R.S. (2016) Molecular Cell, 63:21-33.
(doi: 10.1016/j.molcel.2016.05.020)