Karin M. Reinisch, Ph.D.

Associate Professor of Cell Biology Pew Scholar in the Biomedical Sciences
Phone: (203) 785-6469 Lab: (203) 785-6027 Fax: (203) 785-7446 e-mail: karin dot reinisch at yale dot edu Lab web site: www.cellbiology.yale.edu/reinisch		Department of Cell Biology Yale University School of Medicine 333 Cedar Street PO Box 208002 New Haven, CT 06520-8002 <Courier Address> 333 Cedar Street SHM C-212a/214 New Haven, CT 06510-3206

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My group combines x-ray crystallography with with other biochemical/biophysical techniques to understand the detailed molecular mechanisms that underlie cellular processes. The group currently focuses, first, on understanding protein:RNA interactions that are important in RNA folding and quality control and, second, on better understanding the assembly and regulation of large protein complexes that are involved in secretory trafficking.

For example, in collaboration with the Wolin lab, we have recently elucidated the structure of the Ro protein, both in an unliganded form and an RNA bound form. Ro recognizes misfolded non-coding RNAs, which are not under surveillance of the non-sense mediated decay pathway, and is thought to target them for degradation.  We are interested in which structural determinants of misfolded RNAs Ro recognizes. We are also studying a number of other protein:RNA complexes with a role in RNA quality control or degradation.

Click for a larger image. A space filling representation of the Ro protein in complex with a fragment of Y RNA and single stranded RNA. Ro, a major lupus autoantigen, is normally found bound to a small cytoplasmic RNA, a Y RNA. In the nucleus, Ro also binds to misfolded RNAs and likely targets them for degradation. These misfolded RNAs bind both on the Y RNA binding surface of Ro and, by means of single stranded extensions, in the central cavity of Ro.

Click for a larger image. diffraction image from a crystal of unliganded Ro. The crystal diffracts to beyond 2Å.

With respect to membrane trafficking, we have been collaborating with the laboratory of Peter Novick in studying the assembly and regulation of the exocyst complex. The exocyst, an octameric complex conserved in all eukaryotes from yeasts to humans, docks secretory vesicles to specific regions of the  target membrane in preparation for vesicle fusion. The assembly of the exocyst is highly regulated by a number of small GTPases. We hope that a combination of structural and biochemical information will yield detailed insights into how assembly occurs. Several other projects related to membrane trafficking are also ongoing.

Recent Publications

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Cai, H., Reinisch, K., Ferro-Novick, S. (2007) Coats, Tethers, Rabs and SNAREs work together to mediate the intracellular destination of a transport vesicle.
Dev Cell. 2007 May; 12(5):671-82

Reinisch, KM., Wolin, SL., Emerging themes in non-coding RNA quality control.
Curr Opin Struct Biol. 2007 Apr; 17(2):209-14. Epub 2007 Mar 28.

Dong, G., Medkova, M., Novick, P., Reinisch, KM. A catalytic coiled coil:structural insights into the activation of the Rab GTPase. Sec4p by Sec2p. Mol Cell. 2007 Feb 9; 25(3):455-62.

Cai, H., Yu, S., Menon, S., Cai, Y., Lazarova, D., Fu, C., Reinisch, K., Hay, JC., Feroo-Novick, S.  TRAPPI Tethers COPII vesicles by binding the coat subunit Sec23. Nature. 2007 Feb 22; 445(7130):941-4. Epub 2007 Feb 7.

Fuchs, G., Stein, A.J., Fu, C. , Reinisch, K.M., and Wolin, S.L. (2006) structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen.
Nat Struct Mol Biol. 2006 Nov;13(11):1002-9. Epub 2006 Oct 15.

Dong G, Hutagalung AH, Fu C, Novick P, Reinisch, KM. (2005)  The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif. Nat Struct Mol Biol. 12(12):1094-100.   

Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM. (2005). Structural insights into RNA quality control: The Ro autoantigen binds misfolded RNAs via its central cavity. Cell 121: 529-539. 

Dong G, Chakshusmathi G, Wolin SL, Reinisch KM. (2004)  Structure of the La motif: a winged helix motif mediates RNA binding via a conserved patch. EMBO J. 23(5):1000-7. 

Reinisch KM. (2002)  The dsRNA viridae and their catalytic capsids. Nat Struct Biol 9: 714-716. (News & Views) 

Reinisch KM, Nibert ML, Harrison SC. (2000)  Structure of the reovirus core at 3.6Å resolution. Nature 404: 960-967.  

Luongo CL, Reinisch KM, Harrison SC, Nibert ML. (2000)  Identification of the guanylyl-transferase region and active site in reovirus mRNA capping protein lambda2. J Mol Biol. 275: 2804-2810.  
Reinisch KM, Chen L, Verdine GL, Lipscomb WN. (1995)  The crystal structure of HaeIII methyltransferase covalently complexed to DNA: an extrahelical cytosine & rearranged base pairing. Cell 82(1): 143-153.