title: Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18.
abstract: Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development.
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Peng-Chao
authors.initials: PC
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Huawei
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, 216, Tiansheng Road, Beibei, Chongqing 400716, People's Republic of China.
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry; D015843:Serpins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D015843:Serpins; D012697:Serine Endopeptidases