Structure of mouse muskelin discoidin domain and biochemical characterization of its self-association.
Muskelin is an intracellular kelch-repeat protein comprised of discoidin, LisH, CTLH and kelch-repeat domains. It is involved in cell adhesion and the regulation of cytoskeleton dynamics as well as being a component of a putative E3 ligase complex. Here, the first crystal structure of mouse muskelin discoidin domain (MK-DD) is reported at 1.55 Å resolution, which reveals a distorted eight-stranded β-barrel with two short α-helices at one end of the barrel. Interestingly, the N- and C-termini are not linked by the disulfide bonds found in other eukaryotic discoidin structures. A highly conserved MIND motif appears to be the determinant for MK-DD specific interaction together with the spike loops. Analysis of interdomain interaction shows that MK-DD binds the kelch-repeat domain directly and that this interaction depends on the presence of the LisH domain.
Biomedical Research Institute, Korea Institute of Science and Technology, Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Kook Han
KH
Kim
Biomedical Research Institute, Korea Institute of Science and Technology, Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Seung Kon
SK
Hong
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seoul 136-701, Republic of Korea.
Kwang Yeon
KY
Hwang
Biomedical Research Institute, Korea Institute of Science and Technology, Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Eunice EunKyeong
EE
Kim
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D000070821:Discoidins; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
D015815:Cell Adhesion Molecules; D000070821:Discoidins; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; C503020:Mkln1 protein, mouse; D015800:Protozoan Proteins
CTLH complex; discoidin domain; kelch repeat; muskelin; self-association