Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment


Autoři: Spyros D. Chatziefthimiou aff001;  Philipp Hornburg aff001;  Florian Sauer aff001;  Simone Mueller aff001;  Deniz Ugurlar aff001;  Emma-Ruoqi Xu aff001;  Matthias Wilmanns aff001
Působiště autorů: European Molecular Biology Laboratory, Hamburg Unit, Hamburg, Germany aff001;  University Hamburg Medical Centre Hamburg-Eppendorf, Hamburg, Germany aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226693

Souhrn

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.

Klíčová slova:

Crystal structure – Cysteine – Protein domains – Protein structure – Sequence alignment – Sequence motif analysis – Structural proteins – Sulfates


Zdroje

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