Abstract：
The recently reported structure of the human CNGA1/CNGB1 CNG channel in the open state (Xue et al., 2021a) shows that one CNGA1 and one CNGB1 subunit do not open the central hydrophobic gate completely upon cGMP binding. This is different from what has been reported for CNGA homomeric channels (Xue et al., 2021b; Zheng et al., 2020). In seeking to understand how this difference is due to the presence of the CNGB1 subunit, we find that the deposited density map (Xue et al., 2021a) (EMDB 24465) contains an additional density not reported in the images of the original publication. This additional density fits well the structure of calmodulin (CaM), and it unambiguously connects the newly identified D-helix of CNGB1 to one of the CNGA1 helices (A1R) participating in the coiled-coil region. Interestingly, the CNGA1 subunit that engages in the interaction with this additional density is the one that, together with CNGB1, does not open completely the central gate. The sequence of the D-helix of CNGB1 contains a known CaM-binding site of exquisitely high affinity - named CaM2 (Weitz et al., 1998) -, and thus the presence of CaM in that region is not surprising. The mechanism through which CaM reduces currents across the membrane by acting on the native channel (Bauer, 1996; Hsu and Molday, 1993; Weitz et al., 1998) remains unclear. We suggest that the presence of CaM may explain the partially open central gate reported by Xue et al. (2021a). The structure of the open and closed states of the CNGA1/CNGB1 channel may be different with and without CaM present.
摘要：
最近报道的处于开放状态的人CNGA1/CNGB1CNG通道的结构（Xue等。,2021a）显示，一个CNGA1和一个CNGB1亚基在cGMP结合后不会完全打开中央疏水门。这与CNGA同源通道的报道不同(Xue等人。,2021b；郑等人。,2020）。在试图了解这种差异是如何由于CNGB1亚基的存在，我们发现沉积的密度图(薛等人。,2021a）（EMDB24465）包含原始出版物图像中未报告的额外密度。这种额外的密度非常适合钙调蛋白（CaM）的结构，并且它明确地将新鉴定的CNGB1的D螺旋连接到参与卷曲螺旋区的CNGA1螺旋之一（A1R）。有趣的是,参与与这种额外密度相互作用的CNGA1亚基是，与CNGB1一起，不完全打开中央大门。CNGB1的D-螺旋序列包含一个已知的具有极高亲和力的CaM结合位点-称为CaM2（Weitz等人。,1998)-,因此，CaM在该区域的存在并不令人惊讶。CaM通过作用于天然通道来减少跨膜电流的机制(Bauer，1996年；Hsu和Molday，1993；Weitz等人。,1998）仍然不清楚。我们建议CaM的存在可以解释Xue等人报道的部分打开的中央大门。（2021a）。在存在和不存在CaM的情况下,CNGA1/CNGB1通道的开放状态和封闭状态的结构可以是不同的。
