Collagen recognition and transmembrane signalling by discoidin domain receptors.
Collagen recognition and transmembrane signalling by discoidin domain receptors.
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DOI：
10.1016/j.bbapap.2012.10.014
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发表时间：
2013-10
影响因子：
3.2
通讯作者：
Hohenester, Erhard
中科院分区：
文献类型：
--
作者：
Carafoli, Federico;Hohenester, Erhard
盘状结构域受体DDR1和DDR2是两种密切相关的受体酪氨酸激酶，它们以缓慢和持续的方式被三螺旋胶原激活。DDRs在胚胎发育中具有重要作用，其失调与人类疾病如纤维化、关节炎和癌症有关。DDRs的胞外区由胶原结合盘状蛋白（DS）结构域和DS样结构域组成。跨膜区介导配体非依赖性的DDRs二聚化，并通过异常长的跨膜结构域连接到酪氨酸激酶结构域。纤维状胶原蛋白中的主要DDR结合位点是GVMGFO基序（O是羟脯氨酸），它被DS结构域顶部的两亲性沟槽识别。胶原结合如何导致DDR激活尚不清楚。含有GVMGFO的三螺旋肽以特有的缓慢动力学激活DDR，表明不需要胶原的超分子结构。激活可以通过与DS样结构域结合的单克隆抗体变构阻断。因此，胶原蛋白最有可能引起DDR二聚体内的构象变化，这可能导致形成更大的DDR簇。这篇文章是一个特殊问题的一部分，题为：新兴的识别和激活机制的受体酪氨酸激酶。DDR1和DDR2是由胶原激活的受体酪氨酸激酶。胶原蛋白对DDR的激活是缓慢和持续的。从结构研究中了解胶原蛋白识别的原理。跨膜信号传导的机制目前尚不清楚。讨论了可能的活化机制。
The discoidin domain receptors, DDR1 and DDR2, are two closely related receptor tyrosine kinases that are activated by triple-helical collagen in a slow and sustained manner. The DDRs have important roles in embryo development and their dysregulation is associated with human diseases, such as fibrosis, arthritis and cancer. The extracellular region of DDRs consists of a collagen-binding discoidin (DS) domain and a DS-like domain. The transmembrane region mediates the ligand-independent dimerisation of DDRs and is connected to the tyrosine kinase domain by an unusually long juxtamembrane domain. The major DDR binding site in fibrillar collagens is a GVMGFO motif (O is hydroxyproline), which is recognised by an amphiphilic trench at the top of the DS domain. How collagen binding leads to DDR activation is not understood. GVMGFO-containing triple-helical peptides activate DDRs with the characteristic slow kinetics, suggesting that the supramolecular structure of collagen is not required. Activation can be blocked allosterically by monoclonal antibodies that bind to the DS-like domain. Thus, collagen most likely causes a conformational change within the DDR dimer, which may lead to the formation of larger DDR clusters. This article is part of a Special Issue entitled: Emerging recognition and activation mechanisms of receptor tyrosine kinases. ► DDR1 and DDR2 are receptor tyrosine kinases that are activated by collagen. ► DDR activation by collagen is slow and sustained. ► The principles of collagen recognition are understood from structural studies. ► The mechanism of transmembrane signalling is currently not understood. ► Possible activation mechanisms are discussed.
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DOI：
10.1016/j.str.2009.10.012
发表时间：
2009-12-09
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Carafoli F;Bihan D;Stathopoulos S;Konitsiotis AD;Kvansakul M;Farndale RW;Leitinger B;Hohenester E
通讯作者：
Hohenester E
影响因子：
5.7
作者：
Carafoli, Federico;Mayer, Marie Cathrin;Shiraishi, Kazushige;Pecheva, Mira Anguelova;Chan, Lai Yi;Nan, Ruodan;Leitinger, Birgit;Hohenester, Erhard
通讯作者：
Hohenester, Erhard
影响因子：
28.2
作者：
Hammerman PS;Sos ML;Ramos AH;Xu C;Dutt A;Zhou W;Brace LE;Woods BA;Lin W;Zhang J;Deng X;Lim SM;Heynck S;Peifer M;Simard JR;Lawrence MS;Onofrio RC;Salvesen HB;Seidel D;Zander T;Heuckmann JM;Soltermann A;Moch H;Koker M;Leenders F;Gabler F;Querings S;Ansén S;Brambilla E;Brambilla C;Lorimier P;Brustugun OT;Helland A;Petersen I;Clement JH;Groen H;Timens W;Sietsma H;Stoelben E;Wolf J;Beer DG;Tsao MS;Hanna M;Hatton C;Eck MJ;Janne PA;Johnson BE;Winckler W;Greulich H;Bass AJ;Cho J;Rauh D;Gray NS;Wong KK;Haura EB;Thomas RK;Meyerson M
通讯作者：
Meyerson M
影响因子：
9.8
作者：
Bargal, Ruth;Cormier-Daire, Valerie;Raas-Rothschild, Annick
通讯作者：
Raas-Rothschild, Annick
影响因子：
64.5
作者：
Emsley, J;Knight, CG;Liddington, RC
通讯作者：
Liddington, RC