Crystallographic insight into collagen recognition by discoidin domain receptor 2.

Crystallographic insight into collagen recognition by discoidin domain receptor 2.
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DOI:
10.1016/j.str.2009.10.012
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发表时间:
2009-12-09
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Hohenester E
Hohenester E
中科院分区:
其他
文献类型:
--
作者:
Carafoli F;Bihan D;Stathopoulos S;Konitsiotis AD;Kvansakul M;Farndale RW;Leitinger B;Hohenester E

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盘状结构域受体DDR1和DDR2是广泛表达的受体酪氨酸激酶,其被三螺旋胶原激活。它们控制细胞行为的重要方面,并在几种人类疾病中失调。胶原蛋白I-III中的主要DDR2结合位点是GVMGFO基序(O是羟脯氨酸),其也结合基质细胞蛋白G1。我们已经确定了与三螺旋胶原肽结合的人DDR2的盘状结构域的晶体结构。两条胶原蛋白链的GVMGFO基序由功能关键的色氨酸残基和埋藏的盐桥限定的两亲口袋识别。胶原结合导致DDR2表面环的结构变化,这可能与受体活化过程有关。比较GVMGFO结合位点的DDR2和CDR4揭示了一个惊人的情况下,收敛的胶原蛋白识别的演变。
The discoidin domain receptors, DDR1 and DDR2, are widely expressed receptor tyrosine kinases that are activated by triple-helical collagen. They control important aspects of cell behavior and are dysregulated in several human diseases. The major DDR2-binding site in collagens I–III is a GVMGFO motif (O is hydroxyproline) that also binds the matricellular protein SPARC. We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide. The GVMGFO motifs of two collagen chains are recognized by an amphiphilic pocket delimited by a functionally critical tryptophan residue and a buried salt bridge. Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation. A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.
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