2N10

Solution structure of MyUb (1080-1131) of human Myosin VI

Summary for 2N10

• Entry DOI: 10.2210/pdb2n10/pdb
• Related: 2N0Z 2N11 2N12 2N13 6E5N
• NMR Information: BMRB: 25542
• Descriptor: Unconventional myosin-VI (1 entity in total)
• Functional Keywords: motor protein, protein transport
• Biological source: Homo sapiens (Human)
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein. Isoform 3: Cytoplasmic vesicle, clathrin- coated vesicle membrane. Isoform 4: Cytoplasmic vesicle, clathrin- coated vesicle membrane: Q9UM54
• Total number of polymer chains: 1
• Total formula weight: 7055.11

Authors

He, F.,Ehlinger, A.,Walters, K. (deposition date: 2015-03-20, release date: 2016-03-09, Last modification date: 2024-05-15)

Primary citation

He, F.,Wollscheid, H.P.,Nowicka, U.,Biancospino, M.,Valentini, E.,Ehlinger, A.,Acconcia, F.,Magistrati, E.,Polo, S.,Walters, K.J.
Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains.
Cell Rep, 14:2683-2694, 2016

PubMed Abstract: Myosin VI is critical for cargo trafficking and sorting during early endocytosis and autophagosome maturation, and abnormalities in these processes are linked to cancers, neurodegeneration, deafness, and hypertropic cardiomyopathy. We identify a structured domain in myosin VI, myosin VI ubiquitin-binding domain (MyUb), that binds to ubiquitin chains, especially those linked via K63, K11, and K29. Herein, we solve the solution structure of MyUb and MyUb:K63-linked diubiquitin. MyUb folds as a compact helix-turn-helix-like motif and nestles between the ubiquitins of K63-linked diubiquitin, interacting with distinct surfaces of each. A nine-amino-acid extension at the C-terminal helix (Helix2) of MyUb is required for myosin VI interaction with endocytic and autophagic adaptors. Structure-guided mutations revealed that a functional MyUb is necessary for optineurin interaction. In addition, we found that an isoform-specific helix restricts MyUb binding to ubiquitin chains. This work provides fundamental insights into myosin VI interaction with ubiquitinated cargo and functional adaptors.

PubMed: 26971995
DOI: 10.1016/j.celrep.2016.01.079

Experimental method

SOLUTION NMR