Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors.
Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors.
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DOI：
10.1371/journal.pone.0019682
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Xu HE
中科院分区：
文献类型：
--
作者：
Kumar S;Pioszak A;Zhang C;Swaminathan K;Xu HE
垂体腺苷酸环化酶激活多肽（PACAP）是PACAP/胰高血糖素肽激素家族的一员，控制着免疫、神经、内分泌和肌肉系统的许多生理功能。它通过结合腺苷酸环化酶受体PAC1R激活腺苷酸环化酶，PAC1R是B类g蛋白偶联受体（GPCR）的成员。许多B类GPCR细胞外结构域（ECD）与各自的肽激素结合的晶体结构揭示了激素结合的共识机制。然而，PACAP如何与其受体结合的机制仍然存在争议，因为PAC1R ECD/PACAP复合物的核磁共振结构揭示了ECD的不同拓扑结构和不同的配体识别模式。在这里，我们报告了1.9 Å的PAC1R ECD晶体结构，其采用与其他B类GPCR成员相同的折叠。结合研究和基于细胞的丙氨酸扫描肽和突变受体的实验支持PAC1R使用相同的B类GPCR ECD保守折叠来结合PACAP的模型，从而统一了该受体家族激素结合的共识机制。
Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.
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影响因子：
14.9
作者：
Maiti, R;Van Domselaar, GH;Wishart, DS
通讯作者：
Wishart, DS
影响因子：
3.5
作者：
BUSCAIL, L;GOURLET, P;CHRISTOPHE, J
通讯作者：
CHRISTOPHE, J
DOI：
10.1073/pnas.0801027105
发表时间：
2008-04-01
影响因子：
11.1
作者：
Pioszak, Augen A.;Xu, H. Eric
通讯作者：
Xu, H. Eric
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.
DOI：
10.1073/pnas.0404702101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Grace, CRR;Perrin, MH;Riek, R
通讯作者：
Riek, R