TY  - JOUR
AU  - Chatziefthimiou, Spyros D.
AU  - Hornburg, Philipp
AU  - Sauer, Florian
AU  - Mueller, Simone
AU  - Ugurlar, Deniz
AU  - Xu, Emma-Ruoqi
AU  - Wilmanns, Matthias
TI  - Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment
JO  - PLOS ONE
VL  - 14
IS  - 12
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - PUBDB-2024-00932
SP  - e0226693 -
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 31856237
UR  - <Go to ISI:>//WOS:000534249400059
DO  - DOI:10.1371/journal.pone.0226693
UR  - https://bib-pubdb1.desy.de/record/603747
ER  -