%0 Journal Article
%A Chatziefthimiou, Spyros D.
%A Hornburg, Philipp
%A Sauer, Florian
%A Mueller, Simone
%A Ugurlar, Deniz
%A Xu, Emma-Ruoqi
%A Wilmanns, Matthias
%T Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment
%J PLOS ONE
%V 14
%N 12
%@ 1932-6203
%C San Francisco, California, US
%I PLOS
%M PUBDB-2024-00932
%P e0226693 -
%D 2019
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 31856237
%U <Go to ISI:>//WOS:000534249400059
%R 10.1371/journal.pone.0226693
%U https://bib-pubdb1.desy.de/record/603747