title: Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding.
abstract: The calponin homology-associated smooth muscle (CHASM) protein plays an important adaptive role in smooth and skeletal muscle contraction. CHASM is associated with increased muscle contractility and can be localized to the contractile thin filament via its binding interaction with tropomyosin. We sought to define the structural basis for the interaction of CHASM with smooth muscle tropomyosin as a first step to understanding the contribution of CHASM to the contractile capacity of smooth muscle. Herein, we provide a structure-based model for the tropomyosin-binding domain of CHASM using a combination of hydrogen/deuterium exchange mass spectrometry (HDX-MS) and NMR analyses. Our studies provide evidence that a portion of the N-terminal intrinsically disordered region forms intramolecular contacts with the globular C-terminal calponin homology (CH) domain. Ultimately, cooperativeness between these structurally dissimilar regions is required for CHASM binding to smooth muscle tropomyosin. Furthermore, it appears that the type-2 CH domain of CHASM is required for tropomyosin binding and presents a novel function for this protein domain.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4Z6. jmacdo@ucalgary.ca
authors.forename: Justin A
authors.initials: JA
authors.lastname: MacDonald
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishida
authors.forename: Eric I
authors.initials: EI
authors.lastname: Butler
authors.forename: Annegret
authors.initials: A
authors.lastname: Ulke-Lemée
authors.forename: Mona
authors.initials: M
authors.lastname: Chappellaz
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Tulk
authors.forename: John K
authors.initials: JK
authors.lastname: Chik
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D013058:Mass Spectrometry; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014335:Tropomyosin / Q000737:chemistry / Q000378:metabolism*; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D014335:Tropomyosin; D000096985:Calponins; C491838:SMTNL1 protein, mouse