Thermodynamic And Kinetic Studies Of Protein Structure A

Mcphie, Peter

Abstract

This laboratory is interested in the relationship among protein sequence, structure and the mechanisms of protein folding and enzymic reactions. (i) Secondary Structure of Amyloid Proteins. ? g-factor analysis of the CD spectra of amyloid proteins and polypeptides indicate the presence of two types of structure. Amyloid forms of ovalbumin, apomyoglobin, transthyretin and Ure2p contain 35-55% of beta sheet, whose CD spectrum is like that found in most globular proteins. The more intense spectra of beta-2-microglobulin, insulin, Abeta(1-40) peptide and various homopolypetides, in amyloid films are consistent with the presence of 50-80% of beta helix like structure. The latter result is compatible with a protofibril which contains a structural unit of approximately 45 residues in a beta helix like structure. I am investigating the behavior of peptides known to form anti-parallel sheets as a way to validate these assignments.?

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK024942-14
• Application #: 7334694
• Study Section: (LBG)
• Support Year: 14
• Fiscal Year: 2006

Institution

• Name: U.S. National Inst Diabetes/Digst/Kidney
• Country: United States

Publications

McPhie, Peter; Ni, Yi-sheng; Minton, Allen P (2006) Macromolecular crowding stabilizes the molten globule form of apomyoglobin with respect to both cold and heat unfolding. J Mol Biol 361:7-10

Jang, Ming Y; Yarborough 3rd, Orlando H; Conyers, Gary B et al. (2005) Stable secondary structure near the nicking site for adeno-associated virus type 2 Rep proteins on human chromosome 19. J Virol 79:3544-56

Handa, Vaishali; Yeh, Herman J C; McPhie, Peter et al. (2005) The AUUCU repeats responsible for spinocerebellar ataxia type 10 form unusual RNA hairpins. J Biol Chem 280:29340-5

Britto, P J; Knipling, Leslie; McPhie, Peter et al. (2005) Thiol-disulphide interchange in tubulin: kinetics and the effect on polymerization. Biochem J 389:549-58

Miller, Lance D; McPhie, Peter; Suzuki, Hideyo et al. (2004) Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance. Genome Biol 5:R31

McPhie, Peter (2004) CD studies on films of amyloid proteins and polypeptides: quantitative g-factor analysis indicates a common folding motif. Biopolymers 75:140-7

Kalinin, Andrey E; Idler, William W; Marekov, Lyuben N et al. (2004) Co-assembly of envoplakin and periplakin into oligomers and Ca(2+)-dependent vesicle binding: implications for cornified cell envelope formation in stratified squamous epithelia. J Biol Chem 279:22773-80

Sasahara, Kenji; McPhie, Peter; Minton, Allen P (2003) Effect of dextran on protein stability and conformation attributed to macromolecular crowding. J Mol Biol 326:1227-37

Ahmed, S Ashraf; McPhie, Peter; Smith, Leonard A (2003) Autocatalytically fragmented light chain of botulinum a neurotoxin is enzymatically active. Biochemistry 42:12539-49

Kamiya, Yuji; Puzianowska-Kuznicka, Monika; McPhie, Peter et al. (2002) Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma. Carcinogenesis 23:25-33