NMR structural studies of the myristoylated N-terminus of ADP ribosylation factor 6 (Arf6).
Arf proteins are guanine nucleotide binding proteins that are implicated in endocytotic pathways and vesicle trafficking. The two widely studied isoforms of Arf proteins (Arf1 and Arf6) have different cellular functions and localizations but similar structures. Arf proteins have an N-terminal helix with a covalently bound myristoyl group. Except structural models, there are no three dimensional structures of the myristoylated N-terminal peptide or the intact myristoylated Arf proteins. However, understanding the role of both the myristoyl group and the N-terminal helix based on the details of their molecular structures is of great interest. In the solution structure of myristoylated N-terminal peptide of Arf6 described here, the myristoyl group folds toward the N-terminus to interact with the hydrophobic residues in particular, the phenyl ring. Also, the structure of the dodecylphosphocholine (DPC) micelle-bound of the peptide together with paramagnetic studies showed that the myristoyl group is inserted into the micelle while residues V4-G10 interact with the surface of the micelle. The structural differences between the unbound and micelle-bound myristoylated N-terminal peptide of Arf6 involves the myristoyl group and the side chains of the hydrophobic residues.
Gizachew
Dawit
D
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA. dg58@cornell.edu
Oswald
Robert
R
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D019814:Myristic Acid / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D000089982:ADP-Ribosylation Factor 6; D008823:Micelles; D019814:Myristic Acid; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D020727:ADP-Ribosylation Factors