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Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

Li J, Chen Y, Deng Y, Unarta IC, Lu Q, Huang X, Zhang M
Structure 25 579-591.e4 (2017)
Related entries: 5wst, 5wsu

Cited: 12 times
EuropePMC logo PMID: 28262393

Abstract

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca2+-CaM remains bound to IQ5-SAH, the Ca2+-induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca2+-induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca2+-CaM, suggesting a common Ca2+-induced conformational regulation mechanism.

Reviews citing this publication (1)

  1. Unconventional Myosins: How Regulation Meets Function. Fili N, Toseland CP. Int J Mol Sci 21 E67 (2019)

Articles citing this publication (11)

  1. Effect of Ca2+ on the promiscuous target-protein binding of calmodulin. Westerlund AM, Delemotte L. PLoS Comput Biol 14 e1006072 (2018)
  2. Remarkable Rigidity of the Single α-Helical Domain of Myosin-VI As Revealed by NMR Spectroscopy. Barnes CA, Shen Y, Ying J, Takagi Y, Torchia DA, Sellers JR, Bax A. J Am Chem Soc 141 9004-9017 (2019)
  3. Ca2+-Dependent Switch of Calmodulin Interaction Mode with Tandem IQ Motifs in the Scaffolding Protein IQGAP1. Zhang M, Li Z, Jang H, Hedman AC, Sacks DB, Nussinov R. Biochemistry 58 4903-4911 (2019)
  4. Dynamic ion pair behavior stabilizes single α-helices in proteins. Batchelor M, Wolny M, Baker EG, Paci E, Kalverda AP, Peckham M. J Biol Chem 294 3219-3234 (2019)
  5. Modulating the Stiffness of the Myosin VI Single α-Helical Domain. Barnes CA, Shen Y, Ying J, Bax A. Biophys J 118 1119-1128 (2020)
  6. The shaker-1 mouse myosin VIIa deafness mutation results in a severely reduced rate of the ATP hydrolysis step. Xiong A, Haithcock J, Liu Y, Eusner L, McConnell M, White HD, Belknap B, Forgacs E. J Biol Chem 293 819-829 (2018)
  7. Case Reports Autosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A: A case report and review of the literature. Xia CF, Yan R, Su WW, Liu YH. World J Clin Cases 11 5962-5969 (2023)
  8. Molecular regulatory mechanism of human myosin-7a. Holló A, Billington N, Takagi Y, Kengyel A, Sellers JR, Liu R. J Biol Chem 299 105243 (2023)
  9. Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions. Bai G, Li H, Qin P, Guo Y, Yang W, Lian Y, Ye F, Chen J, Wu M, Huang R, Li J, Lu Y, Zhang M. J Cell Biol 222 e202307117 (2023)
  10. Comparative analysis of the MyTH4-FERM myosins reveals insights into the determinants of actin track selection in polarized epithelia. Matoo S, Graves MJ, Acharya P, Choi MS, Storad ZA, Idris RAES, Pickles BK, Arvay TO, Shinder PE, Gerts A, Papish JP, Crawley SW. Mol Biol Cell 32 ar30 (2021)
  11. Tuning of Liver Sieve: The Interplay between Actin and Myosin Regulatory Light Chain Regulates Fenestration Size and Number in Murine Liver Sinusoidal Endothelial Cells. Zapotoczny B, Szafranska K, Lekka M, Ahluwalia BS, McCourt P. Int J Mol Sci 23 9850 (2022)


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