Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2

Tang, Kun1; Li, Yujie1; Yu, Cong1,2; Wei, Zhiyi1,3

2019-04-12

10.1074/jbc.RA119.007550

JOURNAL OF BIOLOGICAL CHEMISTRY   影响因子和分区

1083351X

1083-351X

Class V myosins are actin-dependent motors, which recognize numerous cellular cargos mainly via the C-terminal globular tail domain (GTD). Myo2, a yeast class V myosin, can transport a broad range of organelles. However, little is known about the capacity of Myo2-GTD to recognize such a diverse array of cargos specifically at the molecular level. Here, we solved crystal structures of Myo2-GTD (at 1.9-3.1 resolutions) in complex with three cargo adaptor proteins: Smy1 (for polarization of secretory vesicles), Inp2 (for peroxisome transport), and Mmr1 (for mitochondria transport). The structures of Smy1- and Inp2-bound Myo2-GTD, along with site-directed mutagenesis experiments, revealed a binding site in subdomain-I having a hydrophobic groove with high flexibility enabling Myo2-GTD to accommodate different protein sequences. The Myo2-GTD-Mmr1 complex structure confirmed and complemented a previously identified mitochondrion/vacuole-specific binding region. Moreover, differences between the conformations and locations of cargo-binding sites identified here for Myo2 and those reported for mammalian MyoVA (MyoVA) suggest that class V myosins potentially have co-evolved with their specific cargos. Our structural and biochemical analysis not only uncovers a molecular mechanism that explains the diverse cargo recognition by Myo2-GTD, but also provides structural information useful for future functional studies of class V myosins in cargo transport.

myosin intracellular trafficking protein-protein interaction protein complex mitochondrial transport peroxisome structural biology X-ray crystallography cargo binding domain enzyme evolution Myo2p MyoVa organelle transport

SCI ; EI

英语

NI论文

第一 ; 通讯

Shenzhen Science and Technology Innovation Commission[JCYJ20160229153100269] ; Shenzhen Science and Technology Innovation Commission[ZDSYS20140509142721429]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000465077500021

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

20191606805683

Binding sites ; C (programming language) ; Crystal structure ; Cytology ; Mammals ; Proteins ; Yeast

Biological Materials and Tissue Engineering:461.2 ; Computer Programming Languages:723.1.1 ; Biochemistry:801.2 ; Organic Compounds:804.1 ; Food Products:822.3 ; Crystal Lattice:933.1.1

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China
2.Shenzhen Key Lab Cell Microenvironm, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen 518055, Peoples R China
3.SUSTech, Neural & Cognit Sci Res Ctr, Shenzhen, Peoples R China

Tang, Kun,Li, Yujie,Yu, Cong,et al. Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(15):5896-5906.

Tang, Kun,Li, Yujie,Yu, Cong,&Wei, Zhiyi.(2019).Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2.JOURNAL OF BIOLOGICAL CHEMISTRY,294(15),5896-5906.

Tang, Kun,et al."Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2".JOURNAL OF BIOLOGICAL CHEMISTRY 294.15(2019):5896-5906.