5FM4

Structure of the C-terminally extended domain My4 of human myomesin (space group P21)

Summary for 5FM4

• Entry DOI: 10.2210/pdb5fm4/pdb
• Related: 5FM5 5FM8
• Descriptor: MYOMESIN-1 (2 entities in total)
• Functional Keywords: structural protein, sarcomere, m-band, fibronectin domain
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 6
• Total formula weight: 73121.80

Authors

Pernigo, S.,Steiner, R.A. (deposition date: 2015-10-30, release date: 2016-11-23, Last modification date: 2024-01-10)

Primary citation

Pernigo, S.,Fukuzawa, A.,Beedle, A.E.,Holt, M.,Round, A.,Pandini, A.,Garcia-Manyes, S.,Gautel, M.,Steiner, R.A.
Binding of Myomesin to Obscurin-Like-1 at the Muscle M-Band Provides a Strategy for Isoform-Specific Mechanical Protection.
Structure, 25:107-120, 2017

PubMed Abstract: The sarcomeric cytoskeleton is a network of modular proteins that integrate mechanical and signaling roles. Obscurin, or its homolog obscurin-like-1, bridges the giant ruler titin and the myosin crosslinker myomesin at the M-band. Yet, the molecular mechanisms underlying the physical obscurin(-like-1):myomesin connection, important for mechanical integrity of the M-band, remained elusive. Here, using a combination of structural, cellular, and single-molecule force spectroscopy techniques, we decode the architectural and functional determinants defining the obscurin(-like-1):myomesin complex. The crystal structure reveals a trans-complementation mechanism whereby an incomplete immunoglobulin-like domain assimilates an isoform-specific myomesin interdomain sequence. Crucially, this unconventional architecture provides mechanical stability up to forces of ∼135 pN. A cellular competition assay in neonatal rat cardiomyocytes validates the complex and provides the rationale for the isoform specificity of the interaction. Altogether, our results reveal a novel binding strategy in sarcomere assembly, which might have implications on muscle nanomechanics and overall M-band organization.

PubMed: 27989621
DOI: 10.1016/j.str.2016.11.015

Experimental method

X-RAY DIFFRACTION (2.8 Å)