This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Giardia lamblia is a water-borne, intestinal pathogen that triggers a form of diarrhea called giardiasis. This early diverging eukaryote infects over 250 million people worldwide and causes a wide range of symptoms from asymptomatic to chronic infection to intestinal malabsorption and weight loss. The life cycle of Giardia switches between the cyst stage when the parasite is first ingested in its water-resistant and dormant form and the trophozoite stage when the cysts are passed to the stomach and released to the small intestine where it attaches, divides and finally completes its life cycle when it is excreted in the feces as infective cysts. After Giardia has inhabited the small intestine, it constantly has to migrate and re-attach to the intestinal epithelium so that the parasite is not swept away since cells in the intestine are continuously being produced and replaced. The flagellum helps in the movement of the parasite while the ventral disk, one of the cytoskeletal components helps the pathogen attach to the epithelium. There is a strong connection between the cytoskeleton and Giardia virulence, since it is the cytoskeleton that helps the parasite move and prevents it from being swept away. Previous research studies have identified the association of cytoskeletal proteins called alpha giardins to the Giardia cytoskeleton. The alpha giardin family consists of 21 members that may play a pivotal role in excystation where the parasite converts from the cyst to the trophozoite form. Currently, we have been able to express, purify and crystallize the first member from the alpha giardin family, alpha-11 giardin. Our structural work on alpha-11 giardin has revealed two new structures, the apo structure of alpha-11 giardin to 1.1 and the calcium-bound structure of alpha-11 giardin to 2.93 , which has revealed a new type of calcium binding site not previously reported before. We wish to continue our structural studies on the alpha giardin family of proteins, which include

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Arts and Sciences
United States
Zip Code
Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; J├Ânsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Morrison, Christine N; Spatzal, Thomas; Rees, Douglas C (2017) Reversible Protonated Resting State of the Nitrogenase Active Site. J Am Chem Soc 139:10856-10862
Zhang, Haonan; Qiao, Anna; Yang, Dehua et al. (2017) Structure of the full-length glucagon class B G-protein-coupled receptor. Nature 546:259-264

Showing the most recent 10 out of 604 publications