title: Nascent structure in the kinase anchoring domain of microtubule-associated protein 2.
abstract: Biological processes are often viewed as highly ordered interactions between well-folded protein domains. The specific interactions exhibited by certain highly abundant neuronal proteins such as microtubule-associated protein 2 (MAP2) and tau stand in stark contrast because these proteins do not show evidence of structure by standard biophysical assays, yet they do bind to specific targets. It is conceivable that there are regions of MAP2 and tau with propensity to form structural domains upon binding a target. To search for evidence of such regions, limited proteolysis experiments were carried out on MAP2c, the smallest MAP2 isoform. Increased protease resistance was observed around the binding site for the RII subunit of cAMP-dependent protein kinase. Protein constructs spanning this region were produced based on the long-lived tryptic fragments Ser44-Arg93 and Ile94-Arg182, and were probed for structure using spectroscopic methods. The results support the existence of regions of nascent structure in the N-terminal region of MAP2c, which are believed to contribute to its regulatory function.
authors.affiliation: Vanderbilt Structural Biology Center, Vanderbilt University, 5142 BIOSCI/MRB III, Nashville, TN 37232-8725, USA.
authors.forename: Anders
authors.initials: A
authors.lastname: Malmendal
authors.forename: Shelley
authors.initials: S
authors.lastname: Halpain
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Chazin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms