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.Signal recognition particles (SRPs) and their receptors function in every domain of life. They are components of an elaborate protein targeting system that delivers newly synthesized proteins to transporters (protein translocases) present in three different membrane systems; the bacterial cytoplasmic membrane, the endoplasmic reticulum, and the chloroplast thylakoid membrane. Malfunction of the SRP targeting/translocation system in humans is implicated in idiopathic inflammatory myopathies, diabetes mellitus, and colon cancer. In bacteria, SRP function is central to the success of bacterial pathogens. Complexities of SRP targeting continue to slow a detailed mechanistic model for how SRP targets and transfers proteins to translocation machinery located in the target membrane. Unique structural and functional features of the more recently discovered chloroplast SRP provide an unprecedented opportunity to examine the SRP targeting mechanism using tools and assays not available or not easily applied to other SRP-based targeting models. A transdisciplinary team led by Goforth and under the mentorship of Henry will apply advanced proteomics and protein structure analysis with more traditional molecular and biochemical approaches in order to (1) identify protein interactions between components of a SRP/receptor/translocase complex, (2) determine the structure of proteins critical for SRP to communicate with receptor and translocase, and (3) determine the function of specific protein/protein interactions in assays that reconstitute each step of the targeting/translocation mechanism. Completion of the proposed work will provide understanding of interactions that (i) are needed for targeting components to engage appropriate and available translocation machinery, (ii) regulate substrate release from SRP to the translocase, and (iii) control release of targeting components from the translocase. Our resulsts will broadly impact our understanding of the molecular machines that function in protein targeting and insertion. Moreover, insight gained through this transdisciplinary approach will provide needed comparative information to identify common mechanistic principals of SRP-based targeting. It is these common features that undoubtedly ensure faithful protein targeting and insertion despite evolutionary forces that have altered the SRP targeting/insertion machinery for efficient operation in a diverse array of organisms and cellular environments.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015569-09
Application #
7719937
Study Section
Special Emphasis Panel (ZRR1-RI-8 (01))
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
9
Fiscal Year
2008
Total Cost
$283,294
Indirect Cost
Name
University of Arkansas at Fayetteville
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
191429745
City
Fayetteville
State
AR
Country
United States
Zip Code
72701
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Prudovsky, Igor; Kacer, Doreen; Davis, Julie et al. (2016) Folding of Fibroblast Growth Factor 1 Is Critical for Its Nonclassical Release. Biochemistry 55:1159-67
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Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu et al. (2014) Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model. Anticancer Drugs 25:30-8
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