Thermodynamic And Kinetic Studies Of Protein Structure

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. (ii) Effect of molecular crowding and confinement on protein satbility (with YiSheng Ni and Allen Minton, NIDDK). Studies on the effect of high concentrations of dextran on the heat and cold denaturation of globular proteins. (iii) Conformational changes produced by nucleic acid/protein interactions.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK024942-13
• Application #: 7151510
• Study Section: (LBG)
• Support Year: 13
• Fiscal Year: 2005

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