Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface.

Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Research Abstract Details 

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Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Abstract Text:

Jonathan R Lai,John D Fisk,Bernard Weisblum,Samuel H Gellman,

The coiled-coil, which consists of two or more interwoven amphiphilic alpha-helices, is formed by sequences that have a characteristic heptad repeat (abcdefg) where a and d are hydrophobic residues. Most efforts to elucidate the origins of coiled-coil pairing selectivity have focused on electrostatic interactions among side chains that flank the core (positions e and g) and on polar side chains that occur occasionally at core positions. We have used phage display to explore another source of coiled-coil specificity: steric matching among nonpolar side chains in the core. We introduced a destabilizing Leu-->Ala mutation into the core of one helix in a known heterodimer and then screened a phage-based library of potential partner helices in search of compensating mutations. We identified a new heterodimer pair (30 residues/helix) that is comparable in stability to the GCN4-p1 homodimer (33 residues/helix). Furthermore, the Leu-->Ala mutant shows specificity for its phage-derived partner over the original partner despite their similar sequences. These results show that a phage-based approach can provide unique insights on coiled-coil pairing preferences that should facilitate both the analysis of natural sequences and the development of specific dimerization motifs that are orthogonal to one another.

Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Publishing Authors By Initials

JR Lai,JD Fisk,B Weisblum,SH Gellman,

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Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 126

Page Numbers: 10514-5

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 1

MONTH: Sep

YEAR: 2004

Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Keywords Mesh Terms:

KEYWORDS: Proteins

MESH TERMS: chemistry

Chemical & Substance for Abstract: Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface. Information

Substance Name: Alanine

Registry Number: 56-41-7

Grant and Affiliation Information for Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface.

AFFILIATION: Graduate Program in Biophysics, University of Wisconsin, Madison, Wisconsin 53706, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61238

ACRONYM: GM

MEDLINETA: J Am Chem Soc

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