Polyproline II helix is a key structural motif of the elastic PEVK segment of titin

K. Ma, L. S. Kan, K. Wang

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Titin is a family of giant elastic proteins that constitute an elastic sarcomere matrix in striated muscle. In the I-band region of the sarcomere, where titin extends and develops passive force upon stretch, titin is composed of tandem repeats of ∼100 residue immunoglobin domains and ∼28-residue PEVK modules. We have performed 2D NMR and circular dichroism (CD) studies of the conformations of one representative 28-mer PEVK module from human fetal titin (PEPPKEVVPEKKAPVAPPKKPEVPPVKV). NMR data of synthetic peptides of this module as well as three constituent peptides of 9 to 12 residues in aqueous solutions reveal distinguishing features for left-handed three-residue per turn PPII helices: the lack of NOE NN(i, i+1), very large NOE αN(i, i+1)/NN(i, i+1), no medium range NOE αN(i, i+2), and dihedral angles φ and ψ values of -78 and 146, respectively. Structural determinations indicate the presence of three short stretches of PPII helices of 4, 5, and 6 residues that are interposed with an unordered, and presumably flexible, spacer region to give one "polyproline II helix-coil" or "PhC" motif for roughly every 10 residues. These peptides also display the characteristic PPII CD spectra: positive peak or negative shoulder band at 223 nm, negative CD band near 200 nm, and biphasic thermal titration curves that reflect varied stability of these PPII helices. We propose that this PhC motif is a fundamental feature and that the number, length, stability, and distribution of PPII is important in the understanding of the elasticity and protein interactions of the PEVK region of titin.

Original languageEnglish
Pages (from-to)3427-3438
Number of pages12
JournalBiochemistry
Volume40
Issue number12
DOIs
Publication statusPublished - Mar 27 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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