Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment.

Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Research Abstract Details 

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Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Abstract Text:

Jason Cellitti,Manuel Llinas,Nathaniel Echols,Elizabeth A Shank,Blake Gillespie,Ester Kwon,Scott M Crowder,Frederick W Dahlquist,Tom Alber,Susan Marqusee,

Small proteins are generally observed to fold in an apparent two-state manner. Recently, however, more sensitive techniques have demonstrated that even seemingly single-domain proteins are actually made up of smaller subdomains. T4 lysozyme is one such protein. We explored the relative autonomy of its two individual subdomains and their contribution to the overall stability of T4 lysozyme by examining a circular permutation (CP13*) that relocates the N-terminal A-helix, creating subdomains that are contiguous in sequence. By determining the high-resolution structure of CP13* and characterizing its energy landscape using native state hydrogen exchange (NSHX), we show that connectivity between the subdomains is an important determinant of the energetic cooperativity but not structural integrity of the protein. The circular permutation results in a protein more easily able to populate a partially unfolded form in which the C-terminal subdomain is folded and the N-terminal subdomain is unfolded. We also created a fragment model of this intermediate and demonstrate using X-ray crystallography that its structure is identical to the corresponding residues in the full-length protein with the exception of a small network of hydrophobic interactions. In sum, we conclude that the C-terminal subdomain dominates the energetics of T4 lysozyme folding, and the A-helix serves an important role in coupling the two subdomains.

Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Publishing Authors By Initials

J Cellitti,M Llinas,N Echols,EA Shank,B Gillespie,E Kwon,SM Crowder,FW Dahlquist,T Alber,S Marqusee,

For similar natural sciences: physics: thermodynamics research abstracts see: natural sciences: physics: thermodynamics research

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Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Journal Published:

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

Journal: Protein science : a publication of the Protein Soc

VOLUME: 16

Page Numbers: 842-51

Journal Abbreviation:

ISSN: 0961-8368

DAY: 30

MONTH: 03

YEAR: 2007

Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Keywords Mesh Terms:

KEYWORDS: Thermodynamics

MESH TERMS: metabolism

Chemical & Substance for Abstract: Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Information

Substance Name: Muramidase

Registry Number: EC 3.2.1.17

Grant and Affiliation Information for Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment.

AFFILIATION: Department of Molecular and Cell Biology and QB3 Institute-Berkeley, University of California, Berkeley, Berkeley, California 94720-3206, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM50945

ACRONYM: GM

MEDLINETA: Protein Sci

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