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Mariah Baker
Baylor College of MedicineDepartment: Molecular Physiology & BiophysicsAddress: One Baylor Plaza, BCM215 Houston, TX 77030 Phone: 713-798-5720 Fax: 713-798-6325 Email: mariahb@bcm.tmc.edu Web: |
Education
B.S. Biology, Environmental Science; Oregon State University (2000)
Honors
2002 Rockwell Scholar
Research Topic
Structural Studies of the Calcium Release Channel
Research Description
The ryanodine receptor (RYR1), a skeletal muscle calcium release channel located in the membrane of the sarcoplasmic reticulum (SR), rapidly transfers calcium from intracellular stores to the cytoplasm necessary for muscle contraction. The channel itself can be regulated by different calcium levels; pCa 5.5 will activate the channel, while pCa below 3 and above 7 are inhibitory. RYR is also regulated by calmodulin (CaM), a broad-range calcium signaling mediator. The channel activity is partially inhibited under Ca2+CaM conditions while under Apo-CaM (Ca2+ free ) conditions the channel is activated. It has been proposed that Apo-CaM and Ca2+CaM have different but structurally close binding sites. Previous studies employing electron cryo-microscopy of RYR and calmodulin revealed a 30� displacement of Apo-CaM and Ca2+CaM. However, a conformational change due to calcium binding to the channel can not be dismissed as a possibility for the displacement. I am currently using electron cryo-microscopy and three dimensional reconstruction techniques to investigate the structural effects of the Ca2+-RYR1-CaM complex using a calcium binding mutant calmodulin, N+3 E1234Q, under channel activating and inactivating conditions. The N+3 E1234Q CaM is a competitive antagonist of CaM for binding to RYR1 at all calcium concentrations and is neither an activator nor inhibitor of the ryanodine receptor.
Selected Publications
- I.I. Serysheva,S. J. Ludtke, M. R. Baker, W. Chiu, and S. L. Hamilton (2002) Structure of the voltage-gated L-type Ca2+ channel by electron cryomicroscopy. PNAS, 99: 10370-10375
Last edited on: August 13, 2009