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- Title
Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment.
- Authors
Chatziefthimiou, Spyros D.; Hornburg, Philipp; Sauer, Florian; Mueller, Simone; Ugurlar, Deniz; Xu, Emma-Ruoqi; Wilmanns, Matthias
- Abstract
In striated muscles, molecular filaments are largely composed of long protein chains with extensive arrays of identically folded domains, referred to as "beads-on-a-string". It remains a largely unresolved question how these domains have developed a unique molecular profile such that each carries out a distinct function without false-positive readout. This study focuses on the M-band segment of the sarcomeric protein titin, which comprises ten identically folded immunoglobulin domains. Comparative analysis of high-resolution structures of six of these domains ‒ M1, M3, M4, M5, M7, and M10 ‒ reveals considerable structural diversity within three distinct loops and a non-conserved pattern of exposed cysteines. Our data allow to structurally interpreting distinct pathological readouts that result from titinopathy-associated variants. Our findings support general principles that could be used to identify individual structural/functional profiles of hundreds of identically folded protein domains within the sarcomere and other densely crowded cellular environments.
- Subjects
PROTEIN domains; STRIATED muscle; COMPARATIVE studies; PROTEINS
- Publication
PLoS ONE, 2019, Vol 14, Issue 12, pN.PAG
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0226693