# 全文"stabilizes/rescue"措辞降级方案

## 依据(见table1_revised.md精确距离分析)
5个受体中只有PAR2(3.21Å)和AGTR2(3.23Å)在真正盐桥范围内,且两者都是工程改造构建体
(thermostabilized/BRIL融合)。CCR2边界(4.16Å,活化态复合物)。EDNRA两态均远超成键距离
(9.16Å/9.59Å),且两个结构(CCR5、EDNRA活化态)的酸性搭档侧链在密度图中未解析,此前报告
的"稳定"距离实际基于不完整侧链的CB级别代理值。

## 逐处替换清单

| 原表述(出现位置) | 新表述 |
|---|---|
| "an acidic residue *within* TM6 that stabilizes Arg6.30" (Abstract) | "an acidic residue within TM6 in candidate proximity to Arg6.30" |
| "Five receptors with experimentally determined structures show a genuine intra-TM6 acidic partner to Arg6.30" (Results §4) | "Five receptors show a candidate intra-TM6 acidic residue near Arg6.30, though heavy-atom distances place only two (PAR2, AGTR2) within salt-bridge range" |
| Table 1 caption "acidic partners" | 保留"partner"作为几何邻近的中性描述,但caption需加入"proximity, not confirmed interaction"的限定 |
| "Local compensation appears graded rather than binary" (Discussion) | 保留,但需注明此判断基于geometry-only证据,非functional |
| "stabilizing Arg6.30 for why equivalent to protecting Arg3.50" 逻辑链 | 需要新增一段解释:即使geometry证实近距离,"stabilizes"到"protects Arg3.50"这一因果链目前没有site-directed mutagenesis或MD证据支持,仅3个案例(GNRHR/P2RY1/PAR2局部螺旋内稳定,见§21.6)有间接功能类比支持,且这些案例本身也未直接验证 |
| 六类"protection mechanism"名称中的"rescue"/"stabilized" | 若在Methods的正式分类命名中出现(如"tm6_intrahelix_stabilized"),需在定义处加脚注:此处"stabilized"是分类标签的历史命名,不代表实验验证的稳定作用,仅描述"存在候选酸性搭档" |

## 新增的Discussion段落(处理"稳定Arg6.30为何等同于保护Arg3.50"这条缺失的机制链)

> "We note an unresolved link in this mechanistic chain: even where a genuine salt-bridge-range
> intra-TM6 acidic partner is confirmed (PAR2, AGTR2), we have not established why stabilizing
> Arg6.30 in this local configuration should be functionally equivalent to protecting the
> DRY-motif Arg3.50 from destabilization — the two residues are on opposite helices (TM3 vs
> TM6) and no direct structural or mutagenesis evidence in this study links the two events.
> The chain assumes that any local anchor for a would-be same-charge clash at 6.30 confers the
> same functional stabilization as the classic cross-helical Arg3.50–Glu6.30 lock; this
> assumption is plausible by analogy to characterized cases in other receptors (e.g., the
> H4R D5.69–R6.31 substitute salt bridge; Discussion literature review) but has not been
> directly tested for any of the five cases reported here."

## 需要同步的Table 1 caption新版本
见table1_revised.md,已包含"candidate intra-TM6 proximity/configuration"替代"stabilizes/rescue"。