Robert M. Stroud, Ph.D.

My group and I have devised approaches to resolve mechanisms in biochemistry at the level of atomic structure. I focus on understanding membrane proteins and targeting of their synthesis. Our membrane protein structures include the first atomic structures of water channels, and of gas channels. These include aquaporins GlpF, AqpZ, the eye lens AQP0, and the H2S channel AQPM, the Plasmodium glycerol transporter, a target for drug discovery, and the human AQP4, deriving the molecular basis for their selectivity. I determined the structure and mechanism of the first ammonia channel at record resolution of 1.35Å followed by the human Rh factor. I was first to develop solvent flattening in 1977 for phasing membrane X-ray profiles. I determined the channel forming colicin Ia and Bacillus thuringiensis toxins that illustrate membrane channel formation. Our crystallization capabilities include robotic systems for optimizing the ultimate resolution of the membrane protein crystals we produce.  Human SLC4 and SLC26 transport proteins are ubiquitously expressed throughout our tissues where they are involved with all cellular biochemical processes. We currently have very little data as to how these human ion transporters function at the atomic level which is very unfortunate given the great potential in this area for drug discovery. Our group at USCF is collaborating with Dr. Kurtz’s team to help solve the structure of various SLC26 transporters.

Relevant and Selected Publications

1.      Newby, Z.E., O’Connell, J.D., 3rd, Gruswitz, F., Hays, F.A., Harries, W.E., Harwood, I.M., Ho, J.D., Lee, J.K., Savage, D.F., Miercke, L.J., Stroud, R.M. (2009) A general protocol for the crystallization of membrane proteins for X-ray structural investigation. Nature Protocols 4, 619-637. (PMID: 19360018; NIHMS151516).

2.      Li, M., Hays, F.A., Roe-Zurz, Z., Vuong, L., Kelly, L., Ho, C.M., Robbins, R.M., Pieper, U., O’Connell, J.D., 3rd, Miercke, L. J., Giacomini, K.M., Sali, A., Stroud, R.M. (2009) Selecting optimum eukaryotic integral membrane proteins for structure determination by rapid expression and solubilization screening. J Mol Biol 385, 820-830. (PMCID: PMC2659619).

3.      Ho, J.D., Yeh, R., Sandstrom, A., Chorny, I., Harries, W.E., Robbins, R.A., Miercke, L.J., & Stroud, R.M. (2009) Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance. Proc Natl Acad Sci USA 106, 7437-7442. (PMCID: PMC2678640).

4.      Gruswitz, F., Chaudhary, S., Ho, J.D., Schlessinger, A., Pezeshki, B., Ho, C.-M., Sali, A., Westhoff, C.M., Stroud, R.M. (2010) Function of human Rh based on structure of RhCG at 2.1 Å. Proc Natl Acad Sci USA. 107, 9638-9643. (PMID: 20457942; PMCID: PMC2906887).

5.      Schlessinger, A., Matsson, P., Shima, J.E., Pieper, U., Yee, S.W., Kelly, L., Stroud, R.M., Ferrin, T.T.E., Giacomini, K.M., Sali, A. (2010) Comparison of human solute carriers. Protein Sci. 19, 412-428. (PMID: 20052679).

6.     Kelly, L., Pieper, U., Eswar, N., Hays, F.A., Li, M., Roe-Zurz, Z., Kroetz, D.L., Giacomini, K.M., Stroud, R.M., Sali, A. (2009) A survey of integral alpha-helical membrane proteins. J Struct Funct Genomics. 10, 269-280 (NIHMS150748).