Help: A Need at Every Level
One of the great gifts of training in acupuncture is the ability to take good care of oneself. I recently had a bout of frozen shoulder — an inflammatory syndrome which can be debilitatingly painful and take years to resolve.
Luckily, I figured out what was happening quickly and started needling nearly every day. Sometimes the needles were placed locally, but often distal points were needled to help pull heat away from the painful site. Some mornings, as soon as I woke up, I could feel the overwhelmed LI 11 points, asking for attention. I’m convinced that acupuncture played a key role in allowing me to fly through the acute stage in about a month and arrive on the other side of frozen shoulder in about six months.
When a patient has become knotted in some unhealthy way, be it frozen shoulder or any other pathology, the work of the acupuncturist may be much more subtle than pounding out the knot. The patient’s whole system may need adjusting, perhaps with a push or pull at quite a distance upstream or downstream from the presenting complaint. It’s not uncommon for a patient to ask why needles would be inserted close to their knees for a digestive symptom. But, when ST36 is employed correctly it helps to un-knot the whole person and improved digestion proceeds naturally from there. This healing art of re-shaping a system so that a healthy conformation can emerge is a marvelous gift, and it is a dynamic we depend on both for healing our diseases and for our foundational health at the cellular level.
There is a whole family of proteins who populate our cells and whose explicit job is to shepherd other proteins through the process of attaining their healthy shape. These helpers are called chaperone proteins, and the proteins they help are referred to as their client proteins. Like patients in an acupuncturist’s office, client proteins may face a number of challenges in their quest to achieve a healthy and functional state.
When proteins are initially assembled, individual amino acids are linked together in a long chain which must fold into a very specific final shape in order to function. Depending on which amino acids are present at any given point in the chain, different properties arise locally. For instance, some amino acids carry a positive charge. A long stretch of these amino acids will make that section of the original string strongly positive, and it will tend to lean toward any negative charge it encounters. There can certainly be a stretch of negative charge elsewhere in the same string, making the protein inclined to bend and hold its negative and positive parts together. What if this would destroy the proper conformation? Imagine another scenario: two distant sections of the chain have to be linked together in order to form a little pocket which is critical to the protein’s eventual function. What will guide those two sections toward one another in a targeted way? The plain fact is that without chaperone proteins, there are client proteins which would never fold correctly — there are too many other, easier conformations to fall into left to chance. Left to themselves, the client proteins would become knotted, dysfunctional, or even pathogenic. Only the targeted care of a chaperone protein allows them to achieve an ordered state.
One chaperone protein with which I have some personal experience is called gp96/GRP94. The name is not inspiring, but its performance truly is. Its clientele includes proteins needed for a wide array of basic cellular function and immunological response. Quite simply, without gp96 none of us would be here; the lack of gp96 is incompatible with even embryonic life. I studied this protein under the direction of Dr. Bei Liu, and recently the two of us were in conversation about some of the mysteries which are still left to solve about this important protein.
At an exacting molecular level, work continues on trying to see the exact way in which the chaperone binds to its client protein, how it guides the client into the correct shape, and how it powers the whole interaction.1,2 Some of these questions have been answered in general for chaperone proteins, and there may be wisdom to be found in how they operate. Chaperone proteins themselves have multiple conformations, and for the purposes of this brief introduction we will look at two. In addition to the chaperone and the client, there is one additional critical component for the work which needs to be done: an energy source. Like most cellular functions which require work, chaperones are powered by the internal currency of the cell, a little energy “pellet” called ATP. When chaperones are ready for a client, they assume conformation 1, opening a slot to take up both an ATP and a client. Once the power supply and client are in place, conformation 2 clicks in and the client is bent as needed. Doing the work of caring for a client burns the ATP and the chaperone then releases both the spent ATP and the newly folded client. The chaperone resets to conformation 1. This is true every single time. The chaperone meets each client fully powered because it re-charges for each interaction. In this way, the chaperone does its critical work without being exhausted.
The chaperone proteins don’t have a choice; they physically can’t engage with their clients without re-powering. On the other hand, health care professionals attempting to guide patients into healthier states can easily out-work power supplies and neglect to re-charge adequately. The built-in sustainability of chaperone proteins is a comfort, considering the degree to which life depends on their function. It may also be a kind of allegory, a molecular meditation on the importance of being a helper and the importance of caring for oneself in order to help others.
- Dollins DE1, Immormino RM, Gewirth DT. Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change. J Biol Chem. 2005 Aug 26;280(34):30438-47. Epub 2005 Jun 11.
- Marzec M1, Eletto D, Argon Y. GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. Biochim Biophys Acta. 2012 Mar;1823(3):774-87. doi: 10.1016/j.bbamcr.2011.10.013. Epub 2011 Nov 3.