Solute Transport across Membranes: -The Structure of a K⁺ Channel Reveals the Basis for Its Specificity

The structure of a potassium channel from the bacterium Streptomyces lividans, determined crystallo graphically by Roderick MacKinnon in 1998, provides much insight into the way ion channels work. This bacterial ion channel is related in sequence to all other known K channels and serves as the prototype for such channels, including the volt age-gated K⁺ channel of neurons. Among the members of this protein family, the similarities in sequence are greatest in the “pore region,” which contains the ion selectivity filter that allows K⁺ (radius 1.33 Å) to pass 10,000 times more readily than Na (radius 0.95 Å)—at a rate (about 108 ions/s) approaching the theoretical limit for unrestricted diffusion. The K⁺ channel consists of four identical subunits that span the membrane and form a cone within a cone surrounding the ion channel, with the wide end of the double cone facing the extracellular space (Fig. 11–48).

FIGURE 11–48 Structure and function of the K channel of Streptomyces lividans. (PDB ID 1BL8) (a) Viewed in the plane of the mem brane, the channel consists of eight transmembrane helices (two from each of the four identical subunits), forming a cone with its wide end toward the extracellular space. The inner helices of the cone (lighter colored) line the transmembrane channel, and the outer helices interact with the lipid bilayer. Short segments of each subunit converge in the open end of the cone to make a selectivity filter. (b) This view perpendicular to the plane of the membrane shows the four subunits arranged around a central channel just wide enough for a single K⁺ ion to pass. (c) Diagram of a K⁺ channel in cross section, showing the structural features critical to function. (See also Fig. 11–49.)

Each subunit has two transmembrane helices as well as a third, shorter helix that contributes to the pore region. The outer cone is formed by one of the trans membrane helices of each subunit. The inner cone, formed by the other four transmembrane helices, sur rounds the ion channel and cradles the ion selectivity filter.

Both the ion specificity and the high flux through the channel are understandable from what we know of the channel’s structure. At the inner and outer plasma membrane surfaces, the entryways to the channel have several negatively charged amino acid residues, which presumably increase the local concentration of cations such as K ⁺ and Na⁺. The ion path through the mem brane begins (on the inner surface) as a wide, water filled channel in which the ion can retain its hydration sphere. Further stabilization is provided by the short helices in the pore region of each subunit, with the partial negative charges of their electric dipoles pointed at K⁺ in the channel. About two-thirds of the way through the membrane, this channel narrows in the region of the selectivity filter, forcing the ion to give up its hydrating water molecules. Carbonyl oxygen atoms in the back bone of the selectivity filter replace the water molecules in the hydration sphere, forming a series of perfect coordination shells through which the K⁺ moves. This favorable interaction with the filter is not possible for Na⁺, which is too small to make contact with all the potential oxygen ligands. The preferential stabilization of K is the basis for the ion selectivity of the filter, and mutations that change residues in this part of the protein eliminate the channel’s ion selectivity. There are four potential K-binding sites along the selectivity filter, each composed of an oxygen “cage” that provides ligands for the K⁺ ions (Fig. 11–49). In the crystal structure, two K⁺ ions are visible within the selectivity filter, about 7.5 Å apart, and two water molecules occupy the unfilled positions. K⁺ ions pass through the filter in single file; their mutual electrostatic repulsion most likely just balances the interaction of each ion with the selectivity filter and keeps them moving. Movement of the two K⁺ ions is concerted: first they occupy positions 1 and 3, then they hop to positions 2 and 4 (Fig. 11–48c). The energetic difference between these two configurations (1, 3 and 2, 4) is very small; energetically, the selectivity pore is not a series of hills and valleys but a flat surface, which is ideal for rapid ion movement through the channel. The structure of the channel appears to have been optimized during evolution to give maximal flow rates and high specificity.

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ملتقى الكوثر الثالث يشهد عرض مشهد حواري بعنوان شريك العمر أم شريك الفكر؟

إقامة مسابقة (مرفأ النور) العلمية للمشاركات في فعاليات ملتقى الكوثر بنسخته الثالثة

ضمن ملتقى الكوثر الثالث.. ورشة تسلط الضوء على بناء الوعي القرآني لدى النساء

شعبة فاطمة بنت أسد (عليها السلام): ملتقى الكوثر منصةً لتحقيق وعي أسري مستند للقرآن الكريم

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نظام غذائي شائع قد يؤدي إلى ارتفاع الكوليسترول الضار

تحذيرات هامة من عواقب تناول "أيبوبروفين" مع أدوية شائعة

علامات مبكرة للإيبولا يمكن الخلط بينها وبين الإنفلونزا

خبراء: الفيروسات مثل هانتا وإيبولا أصبحت أكثر شيوعا وفتكاً

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الليلة.. هلال القمر يلتقي كوكبي الزهرة والمشتري

إيلون ماسك يخسر دعواه القضائية أمام أوبن إيه.آي

مهمة فضائية "أوروبية صينية" لكشف أسرار الرياح الشمسية

انتهاء رحلة "السفينة الموبوءة".. وهذا مصير من بقي على متنها

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