Structural basis of the aberrant receptor binding properties of hagfish and lamprey insulins.
Structural basis of the aberrant receptor binding properties of hagfish and lamprey insulins.
复制标题
DOI：
10.1021/bi901269j
复制
发表时间：
2009-12-01
期刊：
影响因子：
2.9
通讯作者：
De Meyts P
中科院分区：
文献类型：
--
作者：
Sajid W;Holst PA;Kiselyov VV;Andersen AS;Conlon JM;Kristensen C;Kjeldsen T;Whittaker J;Chan SJ;De Meyts P
从结构和生物学角度来看，来自大西洋盲鳗（Myxine hagfish）的胰岛素一直是研究最多的胰岛素之一;然而，其生物学的某些方面仍然存在争议，并且对其低生物学效价没有令人满意的结构解释。我们已经重新研究了受体结合动力学，以及代谢和促有丝分裂的特性，这是一个古老的胰岛素，以及从另一个现存的古代脊索动物的代表，河七鳃鳗（七鳃鳗）。这两种胰岛素与胰岛素类似物具有不寻常的结合动力学和生物学特性，胰岛素类似物在有助于六聚化表面的残基处具有单突变。我们提出并证明了盲鳗和人胰岛素之间的相互氨基酸取代，盲鳗胰岛素的生物活性降低的结果从不利的取代，即，A10（Ile到Arg），B4（Glu到Gly），B13（Glu到Asn），和B21（Glu到瓦尔）。我们同样认为七鳃鳗胰岛素的生物活性改变可能反映了A10（Ile至Lys）、B4（Glu至Thr）和B17（Leu至瓦尔）的取代。八目鳗胰岛素中残基B10处的Asp取代和八目鳗和七鳃鳗胰岛素中残基A8处的His取代可能有助于补偿分子其他区域中的不利变化。这些数据支持这样的概念，即在六聚化表面具有某些突变的胰岛素的一组不寻常的特性可能反映了胰岛素在进化上更接近祖先胰岛素基因产物的那些特性。
The insulin from the Atlantic hagfish (Myxine glutinosa) has been one of the most studied insulins from both a structural and a biological viewpoint; however, some aspects of its biology remain controversial, and there has been no satisfying structural explanation for its low biological potency. We have re-examined the receptor binding kinetics, as well as the metabolic and mitogenic properties, of this phylogenetically ancient insulin, as well as that from another extant representative of the ancient chordates, the river lamprey (Lampetra fluviatilis). Both insulins share unusual binding kinetics and biological properties with insulin analogues that have single mutations at residues that contribute to the hexamerization surface. We propose and demonstrate by reciprocal amino acid substitutions between hagfish and human insulins that the reduced biological activity of hagfish insulin results from unfavorable substitutions, namely, A10 (Ile to Arg), B4 (Glu to Gly), B13 (Glu to Asn), and B21 (Glu to Val). We likewise suggest that the altered biological activity of lamprey insulin may reflect substitutions at A10 (Ile to Lys), B4 (Glu to Thr), and B17 (Leu to Val). The substitution of Asp at residue B10 in hagfish insulin and of His at residue A8 in both hagfish and lamprey insulins may help compensate for unfavorable changes in other regions of the molecules. The data support the concept that the set of unusual properties of insulins bearing certain mutations in the hexamerization surface may reflect those of the insulins evolutionarily closer to the ancestral insulin gene product.
登录
查看更多内容
影响因子：
2.7
作者：
FALKMER, S;MATTY, AJ
通讯作者：
MATTY, AJ
影响因子：
7.7
作者：
DREJER, K;KRUSE, V;GAMMELTOFT, S
通讯作者：
GAMMELTOFT, S
影响因子：
--
作者：
GUARDABASSO, V;RODBARD, D;MUNSON, PJ
通讯作者：
MUNSON, PJ
DOI：
10.1098/rstb.1988.0058
发表时间：
1988-07-06
影响因子：
6.3
作者：
BAKER, EN;BLUNDELL, TL;VIJAYAN, NM
通讯作者：
VIJAYAN, NM
DOI：
10.1016/s0006-291x(73)80072-5
发表时间：
1973-01-01
影响因子：
3.1
作者：
DEMEYTS, P;ROTH, J;LESNIAK, MA
通讯作者：
LESNIAK, MA