Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy.

Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy. Research Abstract Details 

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Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy. Abstract Text:

Wendy S Woods,John M Boettcher,Donghua H Zhou,Kathryn D Kloepper,Kevin L Hartman,Daniel T Ladror,Zhi Qi,Chad M Rienstra,Julia M George,Wendy S Woods,John M Boettcher,Donghua H Zhou,Kathryn D Kloepper,Kevin L Hartman,Daniel T Ladror,Zhi Qi,Chad M Rienstra,Julia M George,Wendy S Woods,John M Boettcher,Donghua H Zhou,Kathryn D Kloepper,Kevin L Hartman,Daniel T Ladror,Zhi Qi,Chad M Rienstra,Julia M George,

alpha-Synuclein (AS) is an intrinsically unstructured protein in aqueous solution but is capable of forming beta-sheet-rich fibrils that accumulate as intracytoplasmic inclusions in Parkinson disease and certain other neurological disorders. However, AS binding to phospholipid membranes leads to a distinct change in protein conformation, stabilizing an extended amphipathic alpha-helical domain reminiscent of the exchangeable apolipoproteins. To better understand the significance of this conformational change, we devised a novel bacteriophage display screen to identify protein binding partners of helical AS and have identified 20 proteins with roles in diverse cellular processes related to membrane trafficking, ion channel modulation, redox metabolism, and gene regulation. To verify that the screen identifies proteins with specificity for helical AS, we further characterized one of these candidates, endosulfine alpha (ENSA), a small cAMP-regulated phosphoprotein implicated in the regulation of insulin secretion but also expressed abundantly in the brain. We used solution NMR to probe the interaction between ENSA and AS on the surface of SDS micelles. Chemical shift perturbation mapping experiments indicate that ENSA interacts specifically with residues in the N-terminal helical domain of AS in the presence of SDS but not in aqueous buffer lacking SDS. The ENSA-related protein ARPP-19 (cAMP-regulated phosphoprotein 19) also displays specific interactions with helical AS. These results confirm that the helical N terminus of AS can mediate specific interactions with other proteins and suggest that membrane binding may regulate the physiological activity of AS in vivo.

Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy. Publishing Authors By Initials

WS Woods,JM Boettcher,DH Zhou,KD Kloepper,KL Hartman,DT Ladror,Z Qi,CM Rienstra,JM George,WS Woods,JM Boettcher,DH Zhou,KD Kloepper,KL Hartman,DT Ladror,Z Qi,CM Rienstra,JM George,WS Woods,JM Boettcher,DH Zhou,KD Kloepper,KL Hartman,DT Ladror,Z Qi,CM Rienstra,JM George,

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Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 34555-67

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 24

MONTH: 09

YEAR: 2007

Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy.

AFFILIATION: Department of Molecular and Integrative Physiology.

Country: United States

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MEDLINETA: J Biol Chem

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