5XPT

Crystal structure of MAD2L2/REV7 in complex with a CAMP fragment in a tetragonal crystal

Summary for 5XPT

• Entry DOI: 10.2210/pdb5xpt/pdb
• Descriptor: Mitotic spindle assembly checkpoint protein MAD2B, Chromosome alignment-maintaining phosphoprotein 1 (3 entities in total)
• Functional Keywords: mad2l2, mad2b, rev7, camp, champ1, transcription-metal binding protein complex, transcription/metal binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q9UI95 Q96JM3
• Total number of polymer chains: 2
• Total formula weight: 28186.58

Authors

Hara, K.,Taharazako, S.,Hashimoto, H. (deposition date: 2017-06-05, release date: 2017-09-20, Last modification date: 2023-11-22)

Primary citation

Hara, K.,Taharazako, S.,Ikeda, M.,Fujita, H.,Mikami, Y.,Kikuchi, S.,Hishiki, A.,Yokoyama, H.,Ishikawa, Y.,Kanno, S.I.,Tanaka, K.,Hashimoto, H.
Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment-maintaining phosphoprotein (CAMP).
J. Biol. Chem., 292:17658-17667, 2017

PubMed Abstract: Mitotic arrest deficient 2-like protein 2 (MAD2L2), also termed MAD2B or REV7, is involved in multiple cellular functions including translesion DNA synthesis (TLS), signal transduction, transcription, and mitotic events. MAD2L2 interacts with chromosome alignment-maintaining phosphoprotein (CAMP), a kinetochore-microtubule attachment protein in mitotic cells, presumably through a novel "WK" motif in CAMP. Structures of MAD2L2 in complex with binding regions of the TLS proteins REV3 and REV1 have revealed that MAD2L2 has two faces for protein-protein interactions that are regulated by its C-terminal region; however, the mechanisms underlying the MAD2L2-CAMP interaction and the mitotic role of MAD2L2 remain unknown. Here we have determined the structures of human MAD2L2 in complex with a CAMP fragment in two crystal forms. The overall structure of the MAD2L2-CAMP complex in both crystal forms was essentially similar to that of the MAD2L2-REV3 complex. However, the residue interactions between MAD2L2 and CAMP were strikingly different from those in the MAD2L2-REV3 complex. Furthermore, structure-based interaction analyses revealed an unprecedented mechanism involving CAMP's WK motif. Surprisingly, in one of the crystal forms, the MAD2L2-CAMP complex formed a dimeric structure in which the C-terminal region of MAD2L2 was swapped and adopted an immature structure. The structure provides direct evidence for the dynamic nature of MAD2L2 structure, which in turn may have implications for the protein-protein interaction mechanism and the multiple functions of this protein. This work is the first structural study of MAD2L2 aside from its role in TLS and might pave the way to clarify MAD2L2's function in mitosis.

PubMed: 28887307
DOI: 10.1074/jbc.M117.804237

Experimental method

X-RAY DIFFRACTION (2.102 Å)