{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Mead AF"],"funding":["NICHD NIH HHS","NHLBI NIH HHS","NINDS NIH HHS","NIAMS NIH HHS","NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere \"C-zone,\" MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development, and promoting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility from the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting MyBP-H may be functionally silent. However, our results suggest an active role. Small angle x-ray diffraction of intact larval tails revealed MyBP-H contributes to the compression of the myofilament lattice accompanying stretch or contraction, while <i>in vitro</i> motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular \"brake\". These results provide new insights and raise questions about the role of the C-zone during muscle development."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.05.10.593199"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11118323"],"repository":["biostudies-literature"],"pubmed_title":["Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle."],"pmcid":["PMC11118323"],"funding_grant_id":["P50 HD103525","R21 NS120419","R01 AR067715","R01 HL157487","S10 OD025030","P30 GM133893","R35 GM141743","S10 OD012331","R01 HL150953"],"pubmed_authors":["Ploysangngam A","Yang L","Previs SB","Kennedy GG","Cipolla MJ","Ebert AM","Gurnett CA","McAdow JF","Warshaw DM","Tremble SM","Mead AF","Wood NB","Palmer BM","Previs MJ","Johnson AN","Nelson SR"],"additional_accession":[]},"is_claimable":false,"name":"Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle.","description":"Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere \"C-zone,\" MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development, and promoting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility from the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting MyBP-H may be functionally silent. However, our results suggest an active role. Small angle x-ray diffraction of intact larval tails revealed MyBP-H contributes to the compression of the myofilament lattice accompanying stretch or contraction, while <i>in vitro</i> motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular \"brake\". These results provide new insights and raise questions about the role of the C-zone during muscle development.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-25T03:27:48.433Z","creation":"2025-08-17T03:06:06.965Z"},"accession":"S-EPMC11118323","cross_references":{"pubmed":["38798399"],"doi":["10.1101/2024.05.10.593199"]}}